Kidney Week

Abstract: FR-PO0781

Concurrent Myeloperoxidase-ANCA Positivity and Type III Mixed Cryoglobulinemia After Tumor Necrosis Factor-α Inhibition

Session Information

• Glomerular Diseases: ANCA Vasculitis, Anti-GBM Disease, and Crescentic GN
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Subahi, Ahmed E., Cleveland Clinic, Cleveland, Ohio, United States

Ahmed E. Subahi, MD

• Tomaszewski, Kristen, Cleveland Clinic, Cleveland, Ohio, United States

Kristen Tomaszewski, MD

• Dweik, Loai, Cleveland Clinic, Cleveland, Ohio, United States

Loai Dweik, MD

• Yedimenko, Juliette, Cleveland Clinic, Cleveland, Ohio, United States

Juliette Yedimenko, MD

• Mehdi, Ali, Cleveland Clinic, Cleveland, Ohio, United States

Ali Mehdi, MD, MEd, FASN

Introduction

Tumor necrosis factor-alpha (TNF-α) inhibitors are common in treating autoimmune and inflammatory disorders but have been linked to paradoxical immune-mediated effects. While ANCA-associated vasculitis and cryoglobulinemia have each been reported with TNF-α inhibitors, concurrent MPO-ANCA positivity and type III mixed cryoglobulinemia are extremely rare. We report such a case in a patient treated with TNF blockade for rheumatoid arthritis.

Case Description

A 71-year-old male with a history of rheumatoid arthritis treated with TNF- α inhibitor therapy, prostate cancer, hypertension, and hyperlipidemia presented with progressive kidney dysfunction over a year (Creatinine up to 3 mg/dL). Urinalysis showed microscopic hematuria and sub-nephrotic range proteinuria with an immune workup revealing a positive perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) with elevated myeloperoxidase (MPO) titers. C3 was normal with a low C4 while rest of the workup was negative. A kidney biopsy was obtained showing a sclerosing glomerulopathy with mild mesangial immune complex deposition. Cryoglobulin testing was positive with polyclonal IgM and IgG cryoglobulins, consistent with type III mixed cryoglobulinemia. Patient’s presentation was felt to be related to immune activation in the context of anti-TNF therapy. TNF-α inhibitor was discontinued , and the patient was started on prednisone and Rituximab. At the last follow-up, creatinine was down to 2.08 mg/dL with a completely bland urine. Cryoglobulins are now negative with normal C4. MPO titers are down from 8 AI to 1.9 AI.

Discussion

This case highlights a rare but important association between TNF α inhibitor therapy and concurrent MPO-ANCA positivity with type III mixed cryoglobulinemia with kidney involvement. Recognition of this paradoxical immune-mediated complication is crucial, as delayed diagnosis may lead to progressive immune complex-mediated organ injury. The patient’s favorable response to Rituximab, with resolution of cryoglobulins, declining ANCA titers, and improvement in kidney function, supports B-cell-directed therapy as a potentially effective treatment strategy in TNF-α inhibitor-associated overlap vasculitic syndromes. Clinicians should maintain a high index of suspicion for secondary autoimmune phenomena in patients receiving TNF- α inhibitors who develop otherwise unexplained kidney dysfunction or systemic inflammatory findings.