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A triad of somatic mutagenesis converges in self-reactive B cells to cause a virus-induced autoimmune disease.
Immunity
January 2025
Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; St Vincent's Clinical School, UNSW Sydney, Sydney, NSW, Australia. Electronic address:
The unexplained association between infection and autoimmune disease is strongest for hepatitis C virus-induced cryoglobulinemic vasculitis (HCV-cryovas). To analyze its origins, we traced the evolution of pathogenic rheumatoid factor (RF) autoantibodies in four HCV-cryovas patients by deep single-cell multi-omic analysis, revealing three sources of B cell somatic mutation converged to drive the accumulation of a large disease-causing clone. A method for quantifying low-affinity binding revealed recurring antibody variable domain combinations created by V(D)J recombination that bound self-immunoglobulin G (IgG) but not viral E2 antigen.
View Article and Find Full Text PDFMyopericarditis in a Patient With Cryoglobulinemic Kidney Disease: A Case Report.
Cureus
December 2024
Nephrology, Ibn Sina Hospital, Rabat, Rabat, MAR.
Cryoglobulinemic vasculitis is a rare small-vessel vasculitis leading to multi-organ dysfunction, often associated with chronic infections like hepatitis C virus (HCV), and autoimmune disorders. Most cases involve mixed monoclonal or polyclonal immunoglobulins, presenting symptoms such as purpura, arthralgias, and weakness. Severe organ involvement, particularly cardiac, is rare but potentially life-threatening.
View Article and Find Full Text PDFSuccessful treatment with bortezomib for refractory cryoglobulinemic vasculitis triggered by ischemic non-obstructive coronary artery disease.
CEN Case Rep
January 2025
Department of Nephrology and Dialysis, Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakae-Cho, Itabashi, Tokyo, 173-0015, Japan.
Article Synopsis
- Type I and mixed cryoglobulinemic vasculitis have different causes, symptoms, and treatment responses, with a reported case of refractory vasculitis linked to ischemic non-obstructive coronary artery disease.
- The patient exhibited severe symptoms including dyspnea, abdominal pain, purpura, and renal failure requiring dialysis, with diagnostic markers suggesting mixed cryoglobulinemia.
- Despite various treatments failing initially, bortezomib and dexamethasone successfully led to clinical improvement and cryoglobulin negativity, indicating bortezomib's potential as an effective therapy for this challenging condition.
Immune checkpoint inhibitors-associated vasculitis: a heterogeneous condition with possible severe disease course.
Rheumatology (Oxford)
December 2024
AP-HP, Université Paris Saclay, department of internal medicine and clinical immunology, Bicêtre Hospital, Le Kremlin Bicêtre, France.
Objective: To describe presentation, treatment and outcome of immune checkpoint inhibitor (ICI) associated-vasculitis in cancer patients in a multicentre study.
Methods: Thanks to the ImmunoCancer International Registry (ICIR), a multidisciplinary network focused on the research of the immune related adverse events related to cancer immunotherapies, patients presenting with a clinical and/or radiological suspicion of vasculitis, and histological evidence of vasculitis after being exposed to ICIs were retrospectively identified.
Results: Twenty eight cases were identified in the ICIR registry.
Non-infectious mixed cryoglobulinemia as a new clinical presentation of mutation in the gene encoding coatomer subunit alpha: a case report of two adult sisters.
Front Immunol
December 2024
Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine-National Research Institute, Warsaw, Poland.
Cryoglobulinemia is a rare disease characterized by the presence of cryoglobulins in the blood serum. It is usually caused by autoimmune, lymphoproliferative, or infectious factors. The pathogenesis of cryoglobulinemia is not well understood, therefore, genetic testing is very important.
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