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Increasing evidence suggested that gut microbiota played critical roles in developing autoimmune diseases. This study investigated the correlation between gut microbiota and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with kidney injury. We analyzed the fecal samples of 23 AAV patients with kidney injury using a 16s RNA microbial profiling approach. The alpha-diversity indexes were significantly lower in AAV patients with kidney injury than healthy controls (Sobs P < 0.001, Shannon P < 0.001, Chao P < 0.001). The beta-diversity difference demonstrated a significant difference among AAV patients with kidney injury, patients with lupus nephritis (LN), and health controls (ANOSIM, p = 0.001). Among these AAV patients, the Deltaproteobacteria, unclassified_o_Bacteroidales, Prevotellaceae , Desulfovibrionaceae Paraprevotella , and Lachnospiraceae _NK4A136_group were correlated negatively with serum creatinine, and the proportion of Deltaproteobacteria, unclassified_o_Bacteroidales, Desulfovibrionaceae , Paraprevotella, and Lachnospiraceae _NK4A136_group had a positive correlation with eGFR. In conclusion, the richness and diversity of gut microbiota were reduced in AAV patients with kidney injury, and the alteration of gut microbiota might be related with the severity of kidney injury of AAV patients. Targeted regulation of gut microbiota disorder might be a potential treatment for AAV patients with kidney injury. [ABSTRACT FROM AUTHOR]

Abstract Background The pathophysiological significance of variable region glycosylation of autoantibodies is still unclear. In the current study, the influence of the variable region N-linked oligosaccharides on the reactivity of three autoantibody specificities was investigated with Sambucus nigra agglutinin (SNA), which mainly binds to oligosaccharides with terminal α2, 6-linked sialic acid on the variable region of IgG. Methods Twenty-seven patients with serum positive anti-neutrophil cytoplasmic autoantibodies (ANCA) against myeploperoxidase (MPO) or proteinase 3 (PR3), or autoantibodies against glomerular basement membrane (GBM) were included. Total IgG was isolated and separated into non-SNA-binding and SNA-binding fractions with SNA affinity chromatography. Antigen-specific IgG was purified by immunoaffinity chromatography. Results At the same concentration of IgG, the antigen binding level of non-SNA-binding IgG was significantly lower than that of SNA-binding IgG for MPO-ANCA (absorbance value at 405 nm, 0.572 ± 0.590 vs. 0.962 ± 0.670, P < 0.001) and for PR3-ANCA (0.362 ± 0.530 vs. 0.560 ± 0.531, P = 0.003). The antigen binding level of non-SNA-binding IgG was significantly higher than that of SNA-binding IgG for anti-GBM antibodies (1.301 ± 0.594 vs. 1.172 ± 0.583, P = 0.044). The level of variable region glycosylation of total IgG was significantly lower than that of affinity-purified MPO-ANCA (1.021 ± 0.201 vs. 1.434 ± 0.134, P = 0.004). The level of variable region glycosylation of total IgG was significantly higher than that of affinity-purified anti-GBM antibodies (1.034 ± 0.340 vs. 0.734 ± 0.333, P = 0.007). The SNA-binding fraction of MPO-ANCA-containing IgG and PR3-ANCA-containing IgG induced higher levels of neutrophil oxygen radical production than the corresponding non-SNA-binding fractions (P < 0.001 and P = 0.043, respectively). The level of variable region glycosylation of affinity-purified MPO-ANCA was higher in active AAV than the same patients in remission (P = 0.001). Conclusion Characteristics of variable region glycosylation of ANCA and anti-GBM antibodies were different from that of total IgG, which might influence the antigen-binding ability of these antibodies. Variable region glycosylation of ANCA might influence the effect of ANCA-induced neutrophils respiratory burst.

Objective. Previous studies have shown that in patients with ANCA-associated vasculitis (AAV), anti-plasminogen antibodies were associated with reduced renal function and the presence of fibrinoid necrosis and cellular crescents in renal histology. The purpose of the current study was to investigate whether anti-plasminogen antibodies are associated with the systemic disease activity of AAV.Methods. One hundred and four Chinese patients with AAV were recruited. Anti-plasminogen antibodies were detected in sequential serum samples at initial onset and remission of the disease. Associations of anti-plasminogen antibodies with clinicopathological parameters were analysed.Results. The prevalence of anti-plasminogen antibodies was significantly higher in AAV patients than in healthy controls (19/104 vs 0/50, χ2 = 8.8, P = 0.003). The prevalence of anti-plasminogen antibodies was significantly higher in the active stage of AAV than in remission (19/104 vs 1/48, χ2 = 7.5, P = 0.013). The level of anti-plasminogen antibodies (expressed as a percentage of the positive controls) correlated with the ESR (r = 0.207, P = 0.042), serum creatinine (r = 0.302, P = 0.002), d-dimer (r = 0.273, P = 0.009) and the percentage of glomeruli with crescents in renal specimens (r = 0.393, P = 0.004). The level of Birmingham vasculitis activity scores and the prevalence of arthralgia and gastrointestinal involvement in patients with anti-plasminogen antibodies were significantly higher than in patients without anti-plasminogen antibodies [22.5 (s.d. 5.63) vs. 19.4 (s.d. 4.66), P = 0.015; 63.2% vs. 25.8%, P = 0.002; 57.9% vs. 21.1%, P = 0.001, respectively].Conclusion. Circulating anti-plasminogen antibodies were associated with systemic disease activity and renal disease activity of AAV. [ABSTRACT FROM PUBLISHER]