Background The combination of anti-glomerular basement membrane (GBM) disease and immunoglobulin A nephropathy (IgAN) has been well documented in sporadic cases, lacking overall assessment in large collections. Herein, we investigated the clinical and immunological characteristics and outcome of this entity. Methods 75 consecutive patients with biopsy-proven anti-GBM disease from March 2012 to March 2020 were screened. Among them, patients with concurrent IgAN were identified and enrolled. The control group included biopsied classical anti-GBM patients during the same period, excluding patients with IgAN, other glomerular diseases or tumors, or patients with unavailable blood samples and missing data. Serum IgG and IgA autoantibodies against GBM were detected by enzyme-linked immunosorbent assay, as were circulating IgG subclasses against GBM. Results 15 patients with combined anti-GBM disease and IgAN were identified, accounting for 20% (15/75) of all patients. Among them, nine were male and six were female, with an average age of 46.7±17.3 years. Thirty patients with classical anti-GBM disease were enrolled as controls, with 10 males and 20 females at an average age of 45.4±15.3 years. Patients with combined anti-GBM disease and IgAN had restricted kidney involvement without pulmonary hemorrhage. Compared with classical patients, anti-GBM patients with IgAN presented with significantly lower levels of serum creatinine on diagnosis (6.2±2.9 v.s. 9.5±5.4mg/dl, P = 0.03) and less occurrence of oliguria/anuria (20%, 3/15 v.s. 57%, 17/30, P = 0.02), but more urine protein excretion [2.37(1.48,5.63) v.s. 1.11(0.63,3.90) g/24h, P = 0.01]. They showed better kidney outcome during follow-up (ESKD: 47%, 7/15 v.s. 80%, 24/30, P = 0.03). The autoantigen and epitope spectrum were comparable between the two groups, but the prevalence of circulating anti-α3(IV)NC1 IgG1(67% v.s. 97%, P = 0.01) and IgG3(67% v.s. 97%, P = 0.01) were lower in patients with IgAN. Conclusions Concurrent IgAN was not rare in anti-GBM disease. Patients showed milder kidney lesions and better recovery after immunosuppressive therapies. It might be partly explained by lower prevalence of anti-GBM IgG1 and IgG3 in these patients.

Background: Anti-glomerular basement membrane disease (GBM) is a kind of chronic autoimmune disease caused by the deposition of circulating anti-GBM antibodies. Non-collagen region of α3 chain of type IV collagen (α3(IV)NC1) is one of the main target antigens. And on α3, EA and EB are the most classical antigen epitopes. It has been reported that anti-GBM antibodies can be detected in HIV patients, but its immunological characteristics are still unclear. In this study, the immunological characteristics of the target antigens were clarified. Methods: Total 93 HIV patients and 20 healthy volunteers were selected in Beijing Youan Hospital from 2017 to 2018. Recombinant human α1-α5(IV)NC1, chimeric protein EA and EB were used as solid phase antigens. Enzyme-linked immunosorbent assay was employed to measure concentrations and subtypes of serum IgG autoantibodies specifically against GBM.Results: Five out of the 93 patients with HIV had low to moderate levels of anti-GBM antibodies. However, these patients presented with no clinical manifestation of any kidney injury or pulmonary hemorrhages. Compared with HIV patients with negative antibodies, there were no significant differences in gender, age, CD4+T cell count and HIV viral load. All sera of five patients recognized non-collagenous domain1 (NC1) of alpha 3 chain of type IV collagen [(α3(IV)NC1] as classic anti-GBM patients, followed by α5(IV)NC1. The antibodies against α3(IV)NC1 were IgG3 predominant, but did not react with either of the classic epitopes on α3 (EA and EB).Conclusion: These data suggest a distinct immunological profile of anti-GBM antibodies in patients with HIV, and might explain the non-pathogenic features of HIV associated anti-GBM antibodies.