IgG4 elevation dilemma at the crossroads of helminth infection and IgG4-related disease: insights from a case report of pediatric paragonimiasis with persistent pericardial effusion
Case Report

IgG4 elevation dilemma at the crossroads of helminth infection and IgG4-related disease: insights from a case report of pediatric paragonimiasis with persistent pericardial effusion

Zhan Zhang, Hua Zhou, Feng Fang, Guo Ai

Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Contributions: (I) Conception and design: Z Zhang, G Ai; (II) Administrative support: H Zhou, F Fang; (III) Provision of study materials or patients: G Ai, H Zhou, F Fang; (IV) Collection and assembly of data: Z Zhang, G Ai; (V) Data analysis and interpretation: Z Zhang, G Ai; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Guo Ai, MD. Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China. Email: aiguotj@sina.com.

Background: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic fibroinflammatory disorder defined by elevated serum IgG4, tissue IgG4+ plasma cell infiltration, and multi-organ involvement. Paradoxically, helminth infections may also trigger IgG4 elevation through Th2-polarized immune responses, creating diagnostic ambiguity when overlapping features occur. Critically, no studies have addressed whether IgG4-RD with helminthiasis can coexist in children or how to differentiate them when histopathology is unavailable.

Case Description: A 10-year-old boy with confirmed pulmonary paragonimiasis developed refractory pericardial effusion and markedly elevated IgG4 [11 g/L, 8.1× upper limit of normal (ULN)]. Despite five courses of praziquantel (75 mg/kg/day), effusions persisted for 8 weeks. Subsequent glucocorticoids (methylprednisolone 2 mg/kg/day) achieved rapid clinical resolution, though lacked histopathology IgG4-RD hallmarks. Longitudinal monitoring revealed a dynamic IgG4 decline (from 11 to 5.25 g/L) post-methylprednisolone therapy. However, residual IgG4 elevation (5.25 g/L, >3× ULN) and absent histopathological features of IgG4-RD left the diagnosis unresolved. Therapeutic monitoring revealed normalized eosinophils and imaging improvement, yet persistent IgG4 suggested potential immune dysregulation beyond parasitic clearance.

Conclusions: This case highlights a critical diagnostic dilemma: IgG4 elevation in parasitic infections may mimic or coexist with IgG4-RD. The rapid glucocorticoid response argues against simple parasitic infections, yet incomplete IgG4 normalization post-treatment leaves coexistence unresolved. Clinicians must weigh these possibilities when anti-helminthic therapy fails, particularly when histopathology is absent. Prospective studies should define pediatric-specific IgG4 thresholds to disentangle infection from autoimmunity.

Keywords: Paragonimiasis; immunoglobulin G4 (IgG4); IgG4-related disease (IgG4-RD); pericardial effusion; case report

Submitted Nov 25, 2024. Accepted for publication May 16, 2025. Published online Jun 25, 2025.

doi: 10.21037/tp-2024-531

Highlight box

Key findings

• Persistent immunoglobulin G4 (IgG4) elevation in pediatric paragonimiasis suggested potential immune dysregulation beyond parasitic clearance. Rapid pericardial effusion resolution with glucocorticoids surpassed anti-parasitic effects. Diagnostic ambiguity due to absent IgG4-related disease (IgG4-RD) histopathology despite meeting serological criteria.

What is known and what is new?

• IgG4 levels are notably elevated in IgG4-RD. Praziquantel is generally effective in more than 90% of cases, and recurrence of paragonimiasis after praziquantel therapy is uncommon.

• First pediatric case showing persistent pericardial effusion and sustained IgG4 elevation post-parasite clearance. The rapid glucocorticoid response (effusion resolution) argues against simple parasitic infections, yet incomplete IgG4 normalization post-treatment leaves the coexistence of parasitic infections and IgG4-RD unresolved.

What is the implication, and what should change now?

• Pediatric IgG4 elevation in Helminth infection requires dual evaluation for infection/autoimmunity. It needed to update guidelines to address infection-autoimmunity overlap.

Introduction

The diagnosis of immunoglobulin G4 (IgG4)-related disease (IgG4-RD) hinges on the triad of serum IgG4 elevation, characteristic histopathology (e.g., storiform fibrosis), and multi-organ involvement per the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD (1). However, helminth infections such as schistosomiasis and paragonimiasis may also induce IgG4 elevation through Th2-polarized immune responses (2,3), creating diagnostic ambiguity when overlapping features occur. This dichotomy stems from IgG4’s dual role: in autoimmunity, it promotes fibrosis via IL-10/TGF-β signaling, whereas, in parasitic infection, it may suppress excessive inflammatory damage through IL-4/IL-13-mediated Th2-polarized responses (4). Such biological contradictions render the clinical interpretation of IgG4 elevation inherently ambiguous, particularly when histopathological evidence is absent, posing significant challenges in differentiating infection from autoimmunity. We first present a pediatric case that epitomizes this diagnostic conundrum: paragonimiasis with persistent pericardial effusion and striking IgG4 elevation refractory to antiparasitic therapy, yet responsive to glucocorticoids. The discordance between therapeutic outcomes (rapid glucocorticoid efficacy vs. praziquantel failure) and incomplete IgG4 normalization challenges conventional diagnostic paradigms, forcing a critical reappraisal of IgG4 biology at the interface of infection and autoimmunity. We present this case in accordance with the CARE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2024-531/rc).

Case presentation

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

A 10-year-old male patient initially presented to the local hospital with complaints of abdominal pain. Given his history of ingesting potentially undercooked crabs two months before this hospitalization, serological screening for parasitic infections was conducted, revealing a positive IgG antibody for Paragonimus species. Hematological analysis indicated a significant elevation in both the proportion (18%) and absolute count (2.03×109/L) of eosinophils. Further diagnostic imaging, including cardiac ultrasound and chest computed tomography (CT), identified the presence of pericardial and pleural effusions. Consequently, a diagnosis of pulmonary paragonimiasis was established, and the patient underwent treatment with approximately five courses of praziquantel within 8 weeks. During this period, the patient exhibited some improvement in symptoms, including abdominal pain, fever, and pericardial and pleural effusions. However, one month post-treatment, a follow-up chest CT scan indicated an increase in the volume of pericardial and pleural effusions, along with the emergence of new pleural effusions in different locations, necessitating the patient’s transfer to our hospital.

Upon admission, the patient’s blood tests showed that both the eosinophil ratio (5.9%) and the absolute count (0.48×109/L) were normal but several abnormalities were found: an accelerated erythrocyte sedimentation rate of 29 mm/h, an elevated total globulin level of 43 g/L, and an increased serum IgG level of 19.1 g/L. Subsequent analysis of IgG subtypes revealed a marked elevation in IgG4 levels, reaching 11 g/L, significantly exceeding the threshold of >1.35 g/L indicative of IgG4-RD. Tests for rheumatoid factor, anti-cyclic citrullinated peptide antibodies, and lupus anticoagulant returned negative results. We also promptly evaluated the patient’s pericardial and pleural effusion levels. Echocardiographic assessment demonstrated separation of the pericardial visceral and parietal layers, with three distinct anechoic regions identified: one measuring 12 mm behind the left ventricular posterior wall, one measuring 12 mm beside the left ventricular lateral wall, and another measuring 5 mm near the apex of the right ventricular free wall. Subsequently, a cardiac magnetic resonance imaging (MRI) scan and functional imaging were conducted on the patient, revealing that the transverse diameter of both atria was 39 mm. The mapping sequence indicated elevated initial T1 and T2 values in the lateral wall and apex of the myocardium, accompanied by a moderate amount of reflux signal shadow within the pericardial cavity (Figure 1). No significant fluid signal was detected on either side of the thoracic cavity. Based on the patient’s medical history, auxiliary examination results, and previous treatment outcomes, after excluding diseases such as viral myocarditis and bacterial infections, we consider that the possibility of IgG4-RD cannot be definitively excluded, even with the concurrent diagnosis of paragonimiasis. Although diagnostic confirmation of IgG4-RD is constrained by the absence of histopathological evidence and is primarily based on elevated IgG4 levels, these limitations are attributable to the constraints of the available examination conditions. Consequently, we initiated a maintenance therapy regimen consisting of praziquantel, supplemented with methylprednisolone (a dosage of 2 mg/kg per day). A follow-up echocardiogram conducted five days post-treatment revealed partial absorption of the pericardial effusion, with the anechoic area reduced to 3 mm behind the left ventricular posterior wall and 8 mm near the apex of the right ventricular free wall, and no significant pleural effusion was observed. Considering that the patient had undergone sufficient antiparasitic therapy for paragonimiasis, praziquantel was discontinued, and maintenance therapy with methylprednisolone was continued, with the dosage gradually reduced to 0.5 mg/kg per day over the subsequent month.

Figure 1 Cardiac MRI and functional imaging before treatment. The initial T1 and T2 values of the myocardium in the upper lateral wall and apex of the mapping sequence were increased. Edema occurred in the left ventricular myocardium, as the arrow indicated (A). The pericardial cavity showed a moderate regurgitation signal. A large amount of effusion can be seen in the pericardial cavity, as the arrow indicated (B). No notable enhancement was detected in the T2 signal of the left ventricular myocardium on the DOUBLE and TRIPLE sequences. The pericardium remains unthickened. There is an increase in epicardial and mediastinal adipose tissue. A moderate presence of reflux signal shadow is evident in the pericardial cavity, while no significant fluid signal is apparent in the bilateral thoracic cavity. Left ventricular function: LVEF 62%, CO 4 L/min, EDVi 69 mL/m2. CO, cardiac output; EDVi, end-diastolic volume index; LVEF, left ventricular ejection fraction; MRI, magnetic resonance imaging.

At a follow-up appointment one month post-discharge, the patient reported an absence of fever, chest tightness, chest pain, or abdominal discomfort. Subsequent blood tests indicated normalization of the erythrocyte sedimentation rate to 2 mm/h, total globulin levels to 33.3 g/L, and serum immunoglobulin levels to 14.7 g/L. A subsequent assessment of IgG subtypes revealed a reduction in the patient’s IgG4 level to 5.25 g/L (compared to the threshold of >1.35 g/L indicative of IgG4-RD). Tests for rheumatic diseases remained negative. Follow-up evaluations using echocardiography and chest ultrasound indicated no significant anechoic areas. Cardiac MRI and functional imaging demonstrated that the pericardial effusion had largely resolved, except for a residual small volume of fluid in the pericardial cavity. The initial T1 and T2 values of the myocardium in the lateral wall and apex were elevated in the mapping sequence, and the left ventricular function of this case improved post-glucocorticoid treatment, thereby not entirely ruling out the potential presence of myocardial edema (Figure 2). The patient’s oral methylprednisolone was gradually tapered, and by the six-month follow-up, the patient had been without medication for approximately 4 months and experienced no significant discomfort.

Figure 2 Cardiac MRI and functional imaging after treatment. The initial T1 and T2 values of the left ventricular myocardium, as assessed by the mapping sequence, appeared normal. The edema of the left ventricular myocardium had decreased compared with before, as the arrow indicated (A). Pericardial effusion had been largely absorbed except for a residual small volume of fluid in the pericardial cavity, as the arrow indicated (B). No discernible abnormalities were detected in the myocardial signals of the left ventricle on both DOUBLE and TRIPLE sequences. The pericardium exhibited no thickening. A minimal amount of effusion was present in the pericardial cavity, while no significant fluid signals were observed in the bilateral thoracic cavity. Left ventricular function: LVEF 69%, CO 5 L/min, EDVi 57 mL/m2. CO, cardiac output; EDVi, end-diastolic volume index; LVEF, left ventricular ejection fraction; MRI, magnetic resonance imaging.

Discussion

The presented case of pediatric paragonimiasis with refractory pericardial effusion and paradoxical IgG4 elevation illuminates the diagnostic and therapeutic challenges at the crossroads of infectious and autoimmune pathologies. This discussion will be systematically analyzed from the following perspectives.

Paragonimiasis, caused by Paragonimus lung flukes, typically manifests with cough, hemoptysis, and pleural effusion. Migration of larvae through tissues can induce effusions in multiple serous cavities, including the pericardium (5). A study (6) involving 57 pediatric patients with paragonimiasis complicated by pericardial effusion revealed that the pericardial effusion in all cases exceeded 10 mm. Following surgical intervention and up to four courses of praziquantel treatment, the pericardial effusion was absorbed in most patients. In a separate study involving 11 pediatric patients diagnosed with paragonimiasis (7), 9 cases developed pleural effusion, while 2 cases exhibited pericardial effusion. In another case report involving a child with paragonimiasis accompanied by pleural effusion and elevated blood IgG4 levels (8), the child’s symptoms improved and did not recur following 3 days of praziquantel treatment and drainage of the pleural effusion. Following the administration of 3 to 4 courses of praziquantel treatment, all patients showed improvement in both hematological parameters and imaging findings. Praziquantel is generally well-tolerated and effective in more than 90% of cases; recurrence of paragonimiasis after praziquantel therapy is uncommon (9), typically linked to incomplete metacercariae eradication or reinfection. However, in the case presented here, five praziquantel courses over 8 weeks exceeded standard regimens [3 to 4 courses recommended (7)], yet effusions recurred, and significant pericardial effusion was detected upon admission to our hospital. Notably, eosinophil levels (a hallmark of active helminthiasis) declined concordantly with normalization (ratio 5.9%, absolute count 0.48×109/L) with antiparasitic therapy, aligning with parasite clearance and paralleling reduced but persistent IgG4 elevation. This dissociation suggests residual IgG4 production may be driven by mechanisms independent of active parasitosis. Besides, eosinophilia is not exclusive to helminth infections and can be observed in other conditions, including allergic reactions, certain malignancies, and autoimmune diseases. Therefore, we discontinued the praziquantel regimen because the efficacy observed so far was not good. Upon cessation of praziquantel and the initiation of monotherapy with methylprednisolone, there was a marked reduction in pericardial effusion, with no recurrence noted during subsequent follow-up. Residual IgG4 elevation post-steroids (5.25 g/L) exceeds levels seen in isolated helminthiasis, hinting at unresolved immune dysregulation. These results suggest that the patient’s clinical trajectory may have involved factors beyond conventional parasitic persistence.

Confusingly, the cause of IgG4 elevation remains unclear: is it due to infection, autoimmunity, or their coexistence? Recent studies suggest that certain helminth infections (e.g., Schistosoma mansoni, filariasis) may transiently elevate IgG4, which often normalizes following antiparasitic therapy (10). In paragonimiasis, transient IgG4 elevation typically normalizes within 4–6 weeks post-treatment (11,12). Strikingly, our case defies this pattern and represents the persistent IgG4 elevation (from 11 to 5.25 g/L) and refractory pericardial effusion in pulmonary paragonimiasis unresponsive to adequate praziquantel treatment-a phenomenon previously unreported in children. The magnitude and duration of IgG4 elevation here exceed reported infection-associated ranges, suggesting potential other causes such as IgG4-RD and so on, except for parasitic infection. This anomaly compels clinicians to reconsider three plausible scenarios: Helminth-derived antigens (e.g., Paragonimus cysteine proteases) may sustain IgG4+ plasma cells via IL-4/IL-13 signaling, independent of ongoing infection (13,14), or shared antigens between parasite and host sustain autoimmune-like reactions (15), or IgG4-RD may coexist with active infection, leading to complex immune cross-reactivity. If adequate anti-infective therapy proves ineffective, the potential presence of comorbidities such as IgG4-RD should be evaluated. In this case, diagnostic treatment with glucocorticoids may be combined with continuous monitoring of disease progression.

While IgG4 levels are notably elevated in IgG4-RD, they may also be elevated in other autoimmune diseases, certain helminth infections in adults, and malignancies (16). During the differential diagnosis of IgG4-RD, it is essential to ensure the exclusion of infectious diseases. Infection by various pathogenic microorganisms, including viruses, bacteria, fungi, and parasites, can result in IgG4-positive plasma cell infiltration or an increase in serum IgG4 concentration, leading to manifestations resembling IgG4-RD. The previous report of parasitic infection with increased blood IgG4 levels is shown in Table 1. The pathogenesis may involve the stimulation of a Th2-type immune response by the infection, with Th2 cell-secreted cytokines promoting the differentiation of B cells into IgG4-positive plasma cells (21). However, the precise mechanisms underlying the IgG4 increase induced by different infections require further investigation to be fully elucidated.

Table 1

List of previous reports of parasitic infection with increased blood IgG4 levels

No. Author Year Infected parasite Patient Blood IgG4 level
(48–1,050 mg/L)		 Pericardial effusions Other major complications Praziquantel treatment Glucocorticoid therapy
Age Gender
1 Taku et al. (8) 2024 Pm 12 years M 1,350 − Pleural effusion Effective No
2 Yin et al. (11) 2025 Pw 40 years F 1,133 − Pleural effusion Effective No
3 Yin et al. (11) 2025 Pw 60 years F Unknown − Multiple cavitary lung lesions; bilateral hydropneumothorax Effective No
4 Saeki et al. (12) 2015 Pw 49 years M 2,010 − Solitary pulmonary nodule; hemosputum Effective No
5 Saeki et al. (12) 2015 Pw 56 years F 3,740 − Cavitary; lesion in the left upper; lobe hemosputum Effective No
6 Ottesen et al. (17) 1985 Filaria 6 months to
65 years		 M/F >1,050 − Paroxysmal nocturnal cough and dyspnea; microfilaremic; elephantiasis of varying degrees Ineffective No
7 Boctor et al. (18) 1990 Sm 12–56 years M Mean ± SD: 8,470±3,420 − Hepatosplenomegaly Effective No
8 Dainichi et al. (19) 2003 Pw 55 years M Unknown − Intracutaneous-subcutaneous tumor; pleural effusion Effective No
9 Chen et al. (20) 2013 Ps 9 years M Unknown − Intracerebral hemorrhage Effective No
10 Chen et al. (20) 2013 Ps 5 years F Unknown − Subpleural mass and pleural effusion in the left lung; subarachnoid hemorrhage Effective No
11 This case 2025 Pw 10 years M 11,000 + Pleural effusions Ineffective Yes

F, female; IgG4, immunoglobulin G4; M, male; Pm, Paragonimus miyazaki; Ps, Paragonimus skrjabini; Pw, Paragonimus westermani; SD, standard deviation; Sm, Schistosoma mansoni.

The etiology and pathogenesis of IgG4-RD have not been fully elucidated. IgG4-RD diagnosis requires serum IgG4 >1.35 g/L, characteristic histopathology (storiform fibrosis, obliterative phlebitis), and multi-organ involvement (1). Pediatric cases of this disease are rarely reported, and there is a paucity of data regarding clinical presentation and treatment in the pediatric population. Previous studies on IgG4-related pulmonary diseases suggest that pulmonary manifestations in patients with IgG4-RD can include pleuritis (22), recurrent pleural effusion (23), inflammatory pseudotumors, interstitial pneumonia (24), and other conditions. These patients generally respond well to corticosteroid therapy. The absence of storiform fibrosis or obliterative phlebitis complicates IgG4-RD diagnosis. However, histopathology has limitations, and emerging evidence suggests that early-stage IgG4-RD or organ-specific variants (e.g., cardiac-limited) may lack classic histopathology (25). In accordance with the RCD criteria for IgG4-RD established in 2020, this patient exhibited suspected myocardial edema and significantly elevated serum IgG4 levels exceeding 135 mg/dL. Although definitive pathological evidence is lacking, a diagnosis of “probable IgG4-RD” could still be considered (1). However, it is crucial to acknowledge that the limitations in the sensitivity and specificity of various diagnostic criteria necessitate cautious application. It should be noted that this clinical diagnosis lacks the basis of histopathological examination. Nevertheless, both adult and pediatric studies currently lack comprehensive data regarding IgG4-RD cardiac involvement. The left ventricular function of this case improved after the addition of glucocorticoid treatment. Our case contributes to the existing clinical data, underscoring the necessity of evaluating potential cardiac involvement in patients suspected of having IgG4-RD.

According to the criteria’s guidelines concerning corticosteroid therapy response, a failure to respond to initial corticosteroid treatment would not support the diagnosis.

Glucocorticoids are almost universally effective in IgG4-RD, at least in the initial exertion of disease control (25). In reviewing the treatment course in this case, a significant response to methylprednisolone therapy was observed; the pericardial effusion did not resolve with the initial administration of adequate antiparasitic treatment but gradually subsided following corticosteroid therapy, thereby supporting the diagnosis of IgG4-RD to a certain extent. Short-term effusion reduction after glucocorticoid therapy exceeds typical anti-parasitic responses. Glucocorticoids may transiently suppress effector Th2 cells without restoring regulatory T cell (Treg) function, permitting IgG4 persistence, while incomplete IgG4 normalization hints at concurrent immune dysregulation. Although the eosinophil levels representing active parasitic infections returned to normal, the residual IgG4 increased (>3× ULN), and we proposed two possibilities: chronic Paragonimus antigens may trigger IgG4-RD-like pathology via molecular mimicry, or true IgG4-RD overlap with paragonimiasis, albeit histologically unproven. Coexisting IgG4-RD may be masked by active infection.

Children exhibit amplified Th2 responses due to fetal immune programming (26), potentially predisposing to exaggerated IgG4 reactions during infection. Our case represents the first report of sustained IgG4 elevation (>3× ULN) in paragonimiasis, suggesting unique host-pathogen interactions. Current IgG4-RD diagnostic thresholds (>1.35 g/L) derive from adult populations, it is essential to consider them within the broader context of clinical and pathological findings (27). Pediatric norms remain undefined, potentially leading to overdiagnosis of IgG4-RD in infection-prone regions. We advocate age-stratified reference ranges and longitudinal IgG4 monitoring in endemic areas.

Conclusions

At present, no studies have investigated the potential correlation between children’s paragonimiasis and the onset of IgG4-RD. This case shatters the diagnostic dichotomy between infectious and immune etiologies of IgG4 elevation. In pediatric populations, developmental Th2 polarization, regional endemicity, and evolving immune memory create a fertile ground for such overlap. The potential overlap in IgG4 elevation between these distinct entities remains unexplored, posing diagnostic challenges as illustrated in this index case, especially in the absence of histopathological evidence. Future research should focus on pediatric-specific diagnostic criteria and studies linking parasitology and autoimmunity to stratify infection-associated IgG4 elevation from true IgG4-RD.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2024-531/rc

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2024-531/prf

Funding: This study was supported by a grant from the Natural Science Foundation of Hubei Province of China (Project No. 2020CFB689).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2024-531/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

  1. Umehara H, Okazaki K, Kawa S, et al. The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD. Mod Rheumatol 2021;31:529-33. [Crossref] [PubMed]
  2. Figueiredo CA, Barreto ML, Rodrigues LC, et al. Chronic intestinal helminth infections are associated with immune hyporesponsiveness and induction of a regulatory network. Infect Immun 2010;78:3160-7. [Crossref] [PubMed]
  3. Wang M, Wu L, Weng R, et al. Therapeutic potential of helminths in autoimmune diseases: helminth-derived immune-regulators and immune balance. Parasitol Res 2017;116:2065-74. [Crossref] [PubMed]
  4. Maslinska M, Dmowska-Chalaba J, Jakubaszek M. The Role of IgG4 in Autoimmunity and Rheumatic Diseases. Front Immunol 2021;12:787422. [Crossref] [PubMed]
  5. Ahn CS, Shin JW, Kim JG, et al. Spectrum of pleuropulmonary paragonimiasis: An analysis of 685 cases diagnosed over 22 years. J Infect 2021;82:150-8. [Crossref] [PubMed]
  6. Wu Y, Zhou Y, Jin X, et al. Diagnosis and surgical management of pericardial effusion due to paragonimiasis. Int J Infect Dis 2019;83:102-8. [Crossref] [PubMed]
  7. Qian M, Li F, Zhang Y, et al. A retrospective clinical analysis of pediatric paragonimiasis in a Chinese children's hospital from 2011 to 2019. Sci Rep 2021;11:2005. [Crossref] [PubMed]
  8. Taku K, Ogata M, Hoshina T, et al. Serial changes in B-cell subsets and immunoglobulin G4 levels in paragonimiasis. Pediatr Int 2024;66:e15727. [Crossref] [PubMed]
  9. Kyung SY, Cho YK, Kim YJ, et al. A paragonimiasis patient with allergic reaction to praziquantel and resistance to triclabendazole: successful treatment after desensitization to praziquantel. Korean J Parasitol 2011;49:73-7. [Crossref] [PubMed]
  10. Matoso LF, Oliveira-Prado R, Abreu MN, et al. Longitudinal analysis of antigen specific response in individuals with Schistosoma mansoni infection in an endemic area of Minas Gerais, Brazil. Trans R Soc Trop Med Hyg 2013;107:797-805. [Crossref] [PubMed]
  11. Yin P, Duan M, Deng L, et al. Initial misdiagnosis to a revised diagnosis of pulmonary paragonimiasis with elevated serum immunoglobulin G4 concentrations: a case report. J Int Med Res 2025;53:3000605251317980. [Crossref] [PubMed]
  12. Saeki S, Horio Y, Hirosako S, et al. Elevated serum IgG4 levels in two cases of paragonimiasis. Respirol Case Rep 2015;3:92-4. [Crossref] [PubMed]
  13. Alghanmi M, Minshawi F, Altorki TA, et al. Helminth-derived proteins as immune system regulators: a systematic review of their promise in alleviating colitis. BMC Immunol 2024;25:21. [Crossref] [PubMed]
  14. Maizels RM, Smits HH, McSorley HJ. Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules. Immunity 2018;49:801-18. [Crossref] [PubMed]
  15. Ruff WE, Dehner C, Kim WJ, et al. Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity. Cell Host Microbe 2019;26:100-113.e8. [Crossref] [PubMed]
  16. Trampert DC, Hubers LM, van de Graaf SFJ, et al. On the role of IgG4 in inflammatory conditions: lessons for IgG4-related disease. Biochim Biophys Acta Mol Basis Dis 2018;1864:1401-9. [Crossref] [PubMed]
  17. Ottesen EA, Skvaril F, Tripathy SP, et al. Prominence of IgG4 in the IgG antibody response to human filariasis. J Immunol 1985;134:2707-12.
  18. Boctor FN, Peter JB. IgG subclasses in human chronic schistosomiasis: over-production of schistosome-specific and non-specific IgG4. Clin Exp Immunol 1990;82:574-8. [Crossref] [PubMed]
  19. Dainichi T, Nakahara T, Moroi Y, et al. A case of cutaneous paragonimiasis with pleural effusion. Int J Dermatol 2003;42:699-702. [Crossref] [PubMed]
  20. Chen Z, Chen J, Miao H, et al. Angiographic findings in 2 children with cerebral paragonimiasis with hemorrhage. J Neurosurg Pediatr 2013;11:564-7. [Crossref] [PubMed]
  21. Garraud O, Perraut R, Riveau G, et al. Class and subclass selection in parasite-specific antibody responses. Trends Parasitol 2003;19:300-4. [Crossref] [PubMed]
  22. Sakata K, Kikuchi J, Emoto K, et al. Refractory IgG4-related Pleural Disease with Chylothorax: A Case Report and Literature Review. Intern Med 2021;60:2135-43. [Crossref] [PubMed]
  23. Murata Y, Aoe K, Mimura Y. Pleural effusion related to IgG4. Curr Opin Pulm Med 2019;25:384-90. [Crossref] [PubMed]
  24. Morales AT, Cignarella AG, Jabeen IS, et al. An update on IgG4-related lung disease. Eur J Intern Med 2019;66:18-24. [Crossref] [PubMed]
  25. Katz G, Stone JH. Clinical Perspectives on IgG4-Related Disease and Its Classification. Annu Rev Med 2022;73:545-62. [Crossref] [PubMed]
  26. Shimizu Y, Tsukada T, Sakata-Haga H, et al. Exposure to Maternal Immune Activation Causes Congenital Unfolded Protein Response Defects and Increases the Susceptibility to Postnatal Inflammatory Stimulation in Offspring. J Inflamm Res 2021;14:355-65. [Crossref] [PubMed]
  27. Baker MC, Cook C, Fu X, et al. The Positive Predictive Value of a Very High Serum IgG4 Concentration for the Diagnosis of IgG4-Related Disease. J Rheumatol 2023;50:408-12. [Crossref] [PubMed]
Cite this article as: Zhang Z, Zhou H, Fang F, Ai G. IgG4 elevation dilemma at the crossroads of helminth infection and IgG4-related disease: insights from a case report of pediatric paragonimiasis with persistent pericardial effusion. Transl Pediatr 2025;14(6):1362-1369. doi: 10.21037/tp-2024-531

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