Elevated IgG4 serum levels in patients with cystic fibrosis

Clerc, A; Reynaud, Quitterie; Durupt, S.; Chapuis‐Cellier, Colette; Nové-Josserand, Raphaële; Durieu, I.; Lega, J.C.

doi:10.1371/journal.pone.0181888

Cited by 13 publications

(8 citation statements)

References 24 publications

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“…This finding may also indicate that the glycosylation pattern of IgG1 DSA interferes with the FcγRs-mediated recognition of the Fc fragment of IgG by immune cells or complement factors. These hypotheses are supported by the observation that only 30% of circulating DSA detected at M1 and at M3 were found to bind C1q in this study cohort and by previous findings that report high IgG4 levels in patients with cystic fibrosis lung disease (59). These data suggest that, in contrast to previous findings, the FCGR3A [158V/V] susceptibility genotype does not appear as a major mechanism of DSA-mediated lung allograft injury.…”

Section: Discussionsupporting

confidence: 89%

“…Although this is a limitation of the study, we cannot exclude the idea that auto-antibodies that target non-HLA antigens which were associated with the development of DSA, such as autoantibodies against K-α1 tubulin (K-α1T) and collagen V (ColV) (64), can participate in the chronic FcR-dependent reaction of recipient cells toward the lung allograft. This is supported by studies that report that development of col (V)-specific TH-17 cells may contribute to the pathogenesis of BOS (25, 59). Indeed, our standardized NK-CHAT evaluation of the DSA induced NK-cell activation was conducted toward B cell lines that express cognate HLA alloantigens.…”

Section: Discussionsupporting

confidence: 55%

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FCGR3A and FCGR2A Genotypes Differentially Impact Allograft Rejection and Patients' Survival After Lung Transplant

et al. 2019

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Fc gamma receptors (FcγRs) play a major role in the regulation of humoral immune responses. Single-nucleotide polymorphisms (SNPs) of FCGR2A and FCGR3A can impact the expression level, IgG affinity and function of the CD32 and CD16 FcγRs in response to their engagement by the Fc fragment of IgG. The CD16 isoform encoded by FCGR3A [158V/V] controls the intensity of antibody-dependent cytotoxic alloimmune responses of natural killer cells (NK) and has been identified as a susceptibility marker predisposing patients to cardiac allograft vasculopathy after heart transplant. This study aimed to investigate whether FCGR2A and FCGR3A polymorphisms can also be associated with the clinical outcome of lung transplant recipients (LTRs). The SNPs of FCGR2A ([131R/H], rs1801274) and FCGR3A ([158V/F], rs396991) were identified in 158 LTRs and 184 Controls (CTL). The corresponding distribution of genotypic and allelic combinations was analyzed for potential links with the development of circulating donor-specific anti-HLA alloantibodies (DSA) detected at months 1 and 3 after lung transplant (LTx), the occurrence of acute rejection (AR) and chronic lung allograft dysfunction (CLAD), and the overall survival of LTRs. The FCGR3A [158V/V] genotype was identified as an independent susceptibility factor associated with higher rates of AR during the first trimester after LTx (HR 4.8, p < 0.0001, 95% CI 2.37–9.61), but it could not be associated with the level of CD16- mediated NK cell activation in response to the LTR's DSA, whatever the MFI intensity and C1q binding profiles of the DSA evaluated. The FCGR2A [131R/R] genotype was associated with lower CLAD-free survival of LTRs, independently of the presence of DSA at 3 months (HR 1.8, p = 0.024, 95% CI 1.08–3.03). Our data indicate that FCGR SNPs differentially affect the clinical outcome of LTRs and may be of use to stratify patients at higher risk of experiencing graft rejection. Furthermore, these data suggest that in the LTx setting, specific mechanisms of humoral alloreactivity, which cannot be solely explained by the complement and CD16-mediated pathogenic effects of DSA, may be involved in the development of acute and chronic lung allograft rejection.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 55%

FCGR3A and FCGR2A Genotypes Differentially Impact Allograft Rejection and Patients' Survival After Lung Transplant

et al. 2019

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“…Immunoglobulin levels were found to increase with age, as well as during pulmonary exacerbations [ 6 ]. An association between chronic colonization with PA and elevated IgG levels and its subtypes was found in several studies [ 3 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 80%

The Association between IgG and Disease Severity Parameters in CF Patients

Gur

Ben-David

Hanna

et al. 2021

JCM

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Assessing disease severity in patients with cystic fibrosis (CF) is essential when directing therapies. Serum immunoglobulin G (IgG) levels increase with disease severity. Lung clearance index (LCI) is recognized as an outcome measure for CF clinical trials. Our aim was to evaluate the correlations between IgG and disease severity markers. This was a single-center retrospective study, evaluating association between IgG and markers of severity in CF patients (including clinical characteristics, lung spirometry, LCI, clinical scores and computed tomography (CT) scores) during stable conditions. There were 69 patients, age 20.5 ± 11.6 years. Nineteen (27.5%) patients had elevated IgG. IgG correlated positively with LCI (r = 0.342, p = 0.005). IgG was higher in pancreatic insufficient (PI) and patients with liver disease (1504.3 ± 625.5 vs. 1229 ± 276.1 mg/dL in PI vs. PS, p = 0.023, and 1702.6 ± 720.3 vs. 1256.2 ± 345.5 mg/dL with vs. without liver disease, p = 0.001, respectively). IgG also correlated positively with CRP, CT score, and days with antibiotics in the previous year (r = 0.38, p = 0.003; r = 0.435, p = 0.001; and r = 0.361, p = 0.002, respectively), and negatively with FEV1% and SK score (r = −0.527, p < 0.001 and r = −0.613, p < 0.001, respectively). IgG correlated with clinical parameters, pulmonary functions, and imaging. However, this is still an auxiliary test, complementing other tests, including lung function and imaging tests. Larger multi-center longitudinal studies are warranted.

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“…28,[116][117][118][119] For example, increased serum IgG4 concentration has been reported in patients with cystic fibrosis who have colonization or infection with Pseudomonas aeruginosa. 141 The imaging findings associated with thoracic IgG4-RD are relatively nonspecific and overlap with several other pathologic processes. When isolated thoracic IgG4-RD is encountered in the absence of extrathoracic disease, histopathologic confirmation will be needed to achieve the diagnosis.…”

Section: Diagnosismentioning

confidence: 99%

Thoracic Involvement in IgG4-Related Disease

Moura

Gripaldo

Baqir

et al. 2020

Semin Respir Crit Care Med

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Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that has been recognized to involve virtually any organ in the body and typically manifests mass-like lesions (tumefactive). Although initial reports of this disease (autoimmune pancreatitis [AIP]) were described in the Japanese population, it has since been reported worldwide. It is most commonly seen in adults of middle age or older, more often men than women. The pathogenesis of IgG4-RD is largely unknown, but genetic factors, microorganisms, and autoimmunity are thought to play important roles. Serum IgG4 concentration is elevated in the majority of patients with IgG4-RD but is a nonspecific finding. Characteristic histopathologic features include dense lymphoplasmacytic infiltrate, fibrosis (often in storiform pattern), and obliterative phlebitis. Lung involvement in IgG4-RD was first reported in 2004 in two patients with AIP and coexisting interstitial lung disease. Since then, a wide spectrum of intrathoracic involvement has been reported and includes not only parenchymal lung diseases but also pleural, airway, vascular, and mediastinal lesions. Thoracic involvement in IgG4-RD is often found incidentally during the workup of extrathoracic lesions but can sometimes be the presenting abnormality. The diagnosis of IgG4-RD requires correlation of clinical, laboratory, imaging, and histopathologic features. Glucocorticoids are the first-line therapy but other options including B cell depletion are being investigated. IgG4-RD is generally associated with an indolent clinical course and most patients improve with glucocorticoid therapy.

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Elevated IgG4 serum levels in patients with cystic fibrosis

Cited by 13 publications

References 24 publications

FCGR3A and FCGR2A Genotypes Differentially Impact Allograft Rejection and Patients' Survival After Lung Transplant

FCGR3A and FCGR2A Genotypes Differentially Impact Allograft Rejection and Patients' Survival After Lung Transplant

The Association between IgG and Disease Severity Parameters in CF Patients

Thoracic Involvement in IgG4-Related Disease

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