Immunoglobulin G4+ clones identified by next-generation sequencing dominate the B cell receptor repertoire in immunoglobulin G4 associated cholangitis

Abstract

BACKGROUND: Racial differences in the treatment of men with localized prostate cancer remain poorly understood. This study examines whether hospital racial composition is associated with the type of treatment black and white men receive. METHODS: The authors performed a retrospective cohort study of men in Surveillance, Epidemiology, and End Results‐Medicare diagnosed with localized prostate cancer from 1995 to 2005 linked to hospital and census data. A total of 134,291 men were assigned to the hospital where they received care. Generalized estimating equations were used to determine whether hospital racial composition was associated with the receipt of definitive therapy and type of treatment. RESULTS: Black men were less likely to receive radiation and/or prostatectomy compared with white men (55.5% vs 63.7%, P < .001) and, among those who received definitive therapy, were less likely to undergo prostatectomy (27.5% vs 31.9%, P < .001). The percentage of black men who received their care at hospitals with a high proportion of black patients was 48.0%, compared with only 5.2% of white patients who received care in this subset of hospitals. Men were significantly less likely to receive definitive treatment (odds ratio, 0.81; 95% confidence interval, 0.74‐0.90) in hospitals with a high proportion of black patients compared with men seen at hospitals with fewer black patients. The association between hospital racial composition and treatment did not significantly differ by patient race. CONCLUSIONS: Hospital racial composition is consistently associated with the care that men receive for localized prostate cancer. Better understanding of the factors that determine where men receive care is an important component in reducing variation in treatment. Cancer 2011;. © 2011 American Cancer Society.

Exposure to occupational antigens might predispose to IgG4‐related disease

“…Our earlier finding of clonal expansions of IgG4‐switched B cells in patients with IgG4‐RD5 is compatible with the presence of an antigen‐driven immune process in these individuals. Given our observed high rate of chronic occupational exposure of two independent cohorts of IgG4‐RD patients suggests that chronic exposure to occupational antigens may play a role in the initiation and/or maintenance of IgG4‐RD in susceptible individuals.…”

“…IgG4, traditionally regarded as a regulatory antibody, has been consistently reported to be upregulated in chronic immune stimulation, as illustrated by an elevation of bee‐venom‐specific IgG4 in beekeepers 4. As reported in this journal, we recently found clonal expansions of IgG4‐switched B‐cells in patients with IAC, using a novel next‐generation sequencing protocol 5. That led us to speculate that chronic antigenic stimulation underlies the often tremendously elevated levels of serum IgG4 in IgG4‐RD.…”

Immunology of IgG4-related disease

“…On the contrary, cerebrospinal fluid analysis of subjects with IgG4-related pachymeningitis revealed the presence of oligoclonal IgG4 bands, suggesting an antigen-driven immune response [85,86]. Indeed, nextgeneration sequencing analysis on biopsy samples and on peripheral blood of IgG4-RD patients demonstrated an oligoclonal expansion of somatically hypermutated IgG4 1 B cell clones, further supporting antigen-specific affinity maturation [76,87].…”

Clonal Characteristics of Circulating B Lymphocyte Repertoire in Primary Biliary Cholangitis

“…In patients with multiple sclerosis, HTS of the Ig repertoire has revealed evidence of clonal expansion and activation of B cells in cerebrospinal fluid (10). Expanded IgG4 + clones were observed in the affected tissue and blood of IgG4-associated cholangitis (11). Analysis of the autoreactive gut plasma cells in celiac disease and their corresponding memory compartment in the peripheral blood using HTS has demonstrated expanded, low somatic hypermutated and biased V region of Ig H chain (IGHV)-containing clones (12).…”