Association of thrombotic microangiopathy and intimal hyperplasia with bleeding post-renal biopsy in antiphospholipid antibody-positive patients.

OBJECTIVE: Renal biopsy remains the gold standard investigation for both diagnostic and prognostic purposes in the clinical management of lupus nephritis. However, it is not without potentially significant complications. The objectives of this study were to determine the rate of significant bleeding post-renal biopsy in patients with lupus nephritis and to identify risk factors associated with hemorrhagic complications. METHODS: Clinical data were retrospectively collected on 215 renal biopsies performed over a 13-year period (1999-2012). Patients were categorized into 3 groups: a diagnosis of systemic lupus erythematosus (SLE) alone, SLE with coexisting antiphospholipid syndrome (APS), or a diagnosis of SLE with either positive anticardiolipin antibodies and/or lupus anticoagulant (LAC) without clinical APS manifestations. RESULTS: Major bleeding complications were significantly more common in those with coexisting APS and/or antiphospholipid antibodies (aPL). LAC, presence of thrombotic microangiopathy (TMA) on renal biopsy, older age at the time of the biopsy (age >40 years), and elevated serum creatinine (>400 µmoles/liter) were independent risk factors for increased risk of bleeding. TMA and severe fibrous intimal hyperplasia on renal biopsy were significantly more prevalent in those who developed severe bleeding complications. CONCLUSION: Based on these findings, lupus nephritis patients with coexisting APS, positive LAC, and histologic evidence of TMA and/or fibrous intimal hyperplasia are at increased risk of bleeding post-renal biopsy. aPL should be checked in all lupus nephritis patients before undergoing renal biopsy, as this subset of patients warrants particular caution pre- and postprocedure.

Granulomatosis with polyangiitis involves sustained mucosal inflammation that is rich in B-cell survival factors and autoantigen.

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is a rare chronic autoimmune disease that may be triggered by upper airway infection. ANCAs specific for PR3 that is expressed by activated neutrophils and macrophages are associated with GPA. Our aim was to investigate regional immune mechanisms that might induce or support the autoimmune response in GPA. METHODS: Biopsy samples from 77 patients including 8 with GPA were studied by immunohistochemistry. B-cell homing subsets in blood samples from 16 patients with GPA and 11 healthy controls were studied by FACS. The distribution of B-cell clones was searched in paired biopsies and blood samples from one patient by analysing immunoglobulin heavy chain gene (IGH) junctional sequences. RESULTS: Activated B cells were located alongside PR3-expressing cells and B-cell survival factors BAFF and APRIL in mucosa from patients with GPA. We detected APRIL production by the granulomas and giant cells. B cells were proliferating in all cases and persistent for 5 years in biopsies obtained from one patient. However, there was no evidence of B-cell clones from the mucosal biopsies circulating in peripheral blood in GPA or any numerical or proportional change in B-cell subsets expressing markers of regional homing in blood in GPA. CONCLUSIONS: Our study illustrates chronically activated B cells alongside autoantigens and B-cell survival factors in the mucosa in GPA.