Abstract: SA-PO195
The Spectrum of Thrombotic Microangiopathy Related to Monoclonal Gammopathy
Session Information
- Onconephrology: Immunological Cross-Talk
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- van Doorn, Daan P.C., Maastricht University Medical Centre+, Department of Nephrology and Clinical Immunology, Maastricht, Limburg, Netherlands
- Timmermans, Sjoerd, Maastricht University Medical Centre+, Department of Nephrology and Clinical Immunology, Maastricht, Limburg, Netherlands
- Abdul-Hamid, Myrurgia, Maastricht Universitair Medisch Centrum+, Maastricht, Limburg, Netherlands
- van Paassen, Pieter, Maastricht University Medical Centre+, Department of Nephrology and Clinical Immunology, Maastricht, Limburg, Netherlands
Group or Team Name
- Limburg Renal Registry, Maastricht UMC+ Center of Expertise for Vasculitis and Immune-Mediated Kidney Disease.
Background
Patients with thrombotic microangiopathy (TMA) should be classified according to etiology to indicate targets for treatment, having impact on treatment and prognosis. Recent studies showed a high prevalence of monoclonal gammopathy (MG) in patients with TMA aged over 50 years. TMA was provisionally added as a MG of renal significance (MGRS) lesion by the International Kidney and MG Research Group. Recent studies suggested that complement dysregulation is common in this group. Here, we studied this premise in 7 patients with TMA and coexisting MG using complement measures, functional ex vivo endothelial cell tests, and genotyping.
Methods
Patients with TMA on kidney biopsy and/or peripheral blood were recruited from the Limburg Renal Registry and prospective COMPETE cohort. Patients with ADAMTS13-activity <10% or Shiga-toxin mediated disease were excluded. Patients were screened for rare variants and rearrangements in complement genes. Massive ex vivo C5b9 formation on endothelial cells, factor H autoantibodies (FHAA) or pathogenic variants in complement genes defined complement dysregulation. IgG was purified from serum to study monoclonal mediated complement activation. As a control, kidney biopsies of 27 patients with MGRS lesions were studied for morphologic features of TMA.
Results
Eighty-four out of 113 patients with TMA were screened for MG. Seven out of 84 patients presented with MG, classified as MGRS (n=6) and multiple myeloma (n=1). MG clustered in patients aged over 50 years (n/N=6/32, 19%). Severe acute kidney injury was noted in all patients. Four out of 7 patients presented with normal complement levels. Serum of one patient induced massive ex vivo C5b9 formation on the endothelium; IgG induced massive ex vivo C3c and C5b9 formation on the perturbed endothelium. Neither IgG nor C4d were found. No pathogenic variants were found. FHAA were present in 2 patients, without homozygous deletion of CFHR3-1. None of the MGRS patients presented with coexisting TMA on kidney biopsy or massive ex vivo C5b9 formation on the endothelium.
Conclusion
MG clustered in patients with TMA aged over 50 years. One patient with MG related TMA presented with alternative pathway activation. We found no evidence of TMA in a MGRS control group. With little evidence for complement dysregulation, the mechanism of MG induced TMA should be studied further.