Background/Purpose: The histopathological findings in IgG4-related disease (IgG4-RD) includes the presence of dense lymphoplasmacytic infiltrate, obliterative phlebitis, storiform fibrosis and the presence of marked IgG4+ plasma cell infiltration observed by immunostaining. The latter has been used in clinical practice only as a diagnostic tool. Whether the number of IgG4+ plasma cells in tissue is associated with any clinical or serological feature has not been previously evaluated. The purpose of this study was to evaluate if the grade of IgG4+ plasma cell infiltration is associated with any clinical or serological outcome.

Methods: We included patients with biopsy proven IgG4-RD according to the Comprehensive Diagnostic Criteria (definitive and probable IgG4-RD) who regularly attended a tertiary referral center in Mexico City (2000-2017). We collected demographics, clinical (organ involvement, relapses and the disease activity assessed by the IgG4-RD Responder Index [IgG4-RD RI] at baseline) as well as baseline laboratory data (C3, C4, total eosinophil count, IgG4 levels). Patients were divided in three groups according to the number of IgG4+ plasma cells in biopsies as follows: <50 IgG4+ plasma cells/HPF, 50-100 IgG4+ plasma cells/HPF, and >100 IgG4+ plasma cells/HPF.

Results:

We included 30 patients, 17 (56.6%) women, mean age 53 ± 13.9 years and median disease duration 13 months. The biopsies were from the following tissues: lacrimal gland (n=6), pancreas (n=5), orbit (n=4), kidney (n=4), lymph node (n=3), mediastinum (n=2), salivary gland (n=2) and other tissues (n=4). Eleven patients (36.6%) had <50 IgG4+ plasma cells/HPF, 9 patients (30%) 50-100 IgG4+ plasma cells/HPF and 10 (33.3%) patients >100 IgG4+ plasma cells/HPF. We did not find any difference regarding age, gender, time of follow up, number of involved organs and relapses. The median baseline IgG4-RD RI was 9, 6 and 15, for the <50 IgG4+ plasma cells/HPF, 50-100 IgG4+ plasma cells/HPF, and >100 IgG4+ plasma cells/HPF groups respectively, however, there was not a statistical difference. The group with >100 IgG4+ plasma cells/HPF had more frequently lymphadenopathy when compared with the other groups (36.4%, 66.7% and 80%, p=0.02; respectively) while the proportion of involvement of the remaining anatomic sites were similar. We found a statistical difference in serum C3 levels (99.5 mg/dl, 159 mg/dl, 78.5 mg/dl, p=0.04) and a tendency for serum C4 levels (20 mg/dl, 27 mg/dl, and 6 mg/dl, p=0.08) among the groups with >100 and ≤ 100 IgG4+ plasma cells/HPF, respectively; whereas the levels of serum IgG4 and the eosinophil count were similar. The C3 and C4 serum levels negatively correlated with the basal IgG4-RD RI (t=-0.48, p=0.005 and t=-0.58, p=0.001).

Conclusion: Our results show that the number of IgG4+ plasma cells observed by immunostaining in IgG4-RD may be of value in identifying a subset of patients with hypocomplementemia, lymphadenopathy and higher baseline disease activity. The finding of an association between hypocomplementemia and higher tissue infiltration by IgG4+ plasma cells expands the evidence that complement activation may contribute to the pathogenesis of IgG4-RD.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/is-the-number-of-igg4-plasma-cells-observed-by-immunostaining-important-beyond-its-diagnostic-utility-in-igg4-related-disease/