Waldenstrom macroglobulinaemia with AA amyloidosis reveals a B-cell-restricted NLRP2 variant

First author: Terré et al.

Link to article: DOI: 10.1111/bjh.19383

Summary

Waldenström macroglobulinemia (WM) is a rare malignant hematopathy characterized by lymphoplasmacytic lymphoma (LPL) secreting IgM. Some patients with WM exhibit chronic inflammation, sometimes complicated by AA amyloidosis, which involves the deposition of insoluble fibrils derived from serum amyloid A (SAA) protein. However, the underlying mechanism of this inflammation remains poorly understood.

We report the case of an 86-year-old female patient with WM complicated by AA amyloidosis. Whole-exome sequencing (WES) revealed a somatic mutation in NLRP2 restricted to B cells. We investigated the functional consequences of this mutation.

The analyses showed that the NLRP2 p.Asp121Gly mutation leads to a reduction in ASC aggregation, a marker of inflammasome activation. In a WM model, the loss of NLRP2 resulted in an increased secretion of CCL-5, a cytokine promoting IL-6 production by stromal cells. IL-6 is a key factor in the induction of SAA, and our results suggest that the NLRP2 mutation may have contributed to the development of AA amyloidosis in this patient.

These findings highlight the importance of somatic mutations in inflammatory regulation and the need for further studies to clarify the role of NLRP2 in the pathophysiology of inflammatory WM (IWM).

Waldenstrom macroglobulinaemia with AA amyloidosis reveals a B‐cell‐restricted NLRP2 varia.

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Acute tubulointerstitial nephritis and renal amyloidosis: A rare complication of Atezolizumab

First author: Naqib Ullah

Journal: Cureus

Reference : DOI : 10.7759/cureus.49533

Link to article: https://pubmed.ncbi.nlm.nih.gov/38156149/

Introduction:

Lung cancer is the second most common malignancy. The two types of lung cancer are small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Among current treatments, anti-PD-1 or anti-PD-L1 agents (checkpoint inhibitors (PKIs): pembrolizumab and atezolizumab) represent adjuvant therapy in lung cancer. The most frequently reported adverse events with ICPs are diarrhea, pneumopathy and drug-induced hepatitis.

The authors report here the case of a 70-year-old man who received Atezolizumab as adjuvant therapy and developed nephrotic-like proteinuria, revealing AA amyloidosis and atezolizumab-induced interstitial nephritis.

Résumé Article Néphrite tubulointerstitielle aiguë et amylose rénale.pdf

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Anakinra-Associated Systemic Amyloidosis

First author: S Alehashemi

Journal : Arthritis and Rheumatology

Reference : DOI : 10.1002/art.42664

Link to article: https://pubmed.ncbi.nlm.nih.gov/37488949/

This article reports the first case of iatrogenic systemic amyloidosis due to prolonged use of anakinra, an interleukin-1 receptor antagonist (IL-1Ra), in a patient suffering from multisystem inflammatory disease of neonatal onset (NOMID).

After several years of treatment with daily injections, the patient developed nodules at the injection site, a nephrotic syndrome and amyloid deposits in various organs (skin, kidney, stomach). Mass spectrometry analysis identified these deposits as being due to recombinant anakinra protein, distinct from the endogenous version.

This case highlights a rare complication of injectable biologic treatments, exacerbated by high and prolonged doses. It highlights the importance of monitoring serum protein levels, varying injection sites, and considering a change of therapy if anakinra-related amyloidosis is diagnosed.

Résumé Article Amylose AA Anakinra.pdf

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