Immunological repertoire linked to PSTPIP1-associated myeloid-related inflammatory (PAMI) syndrome

Abstract

Background Mutations along PSTPIP1 gene are associated to two specific conditions, PAPA syndrome and PAMI syndrome, both autoinflammatory disorders associated to disturbances in cytoskeleton formation. Immunological aspects of PAMI syndrome has not yet been reported neither the clinical impact on therapeutical decisions. Methods Clinical data of patients records were retrospectively accessed. Genomic DNA were extracted and sequenced following standard procedures. Peripheral lymphocytes were quantified in T, B e FOXP3 phenotypes. Results We describe two related patients with PAMI syndrome harboring the usual E250K mutation. Anti-IL1 therapy could partially control the disease in the index patient. A broad spectrum of immunological effects as well as an aberrant expression of FOXP3 could be observed. Conclusions Here we report two related brazilian patients with PAMI syndromes harboring the E250K mutation in PSTPIP1, their immunological aspects and the therapeutical response to canakinumab.

PSTPIP1-Associated Myeloid-Related Proteinemia Inflammatory (PAMI) Syndrome: A Systematic Review

“…Our review identified 252 articles through database searches. After eliminating duplicates and excluding unqualified articles, we included 25 relevant articles that described 43 patients with PAMI syndrome [ 1 , 2 , 3 , 5 , 6 , 7 , 8 , 9 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ].…”

“…Interestingly, phenotypic heterogeneity was observed among family members sharing the same variants [ 2 , 3 , 19 , 21 , 29 ]. In most patients, clinical symptoms appeared gradually over a period of several years.…”

“…While primarily affecting these areas, our review highlighted that other organs may also be affected considerably. Several authors have reported gastrointestinal involvement, with 16% of cases experiencing flare-ups of colitis and/or chronic diarrhea [ 3 , 16 , 19 , 20 , 24 , 28 , 29 ]. Notably, 57% of these patients developed the disease within the first few months of life, suggesting that PAMI syndrome should be considered in the differential diagnosis of early onset inflammatory bowel disease (IBD).…”

“…However, the efficacy of anti-TNF agents was more often observed in a combination treatment with steroids and/or cDMARDs, while anti-IL-1 therapy seems to be more frequently effective as a monotherapy. Notably, anti-IL-1 therapy has shown promising efficacy even for severe manifestations involving the neurologic, gastrointestinal and renal systems [ 19 , 22 , 23 ]. Our review also suggests that there may also be a role for NSAID, corticosteroids, or cyclosporine in the symptomatic treatment of this condition.…”

Clinical and Genetic Findings of the First Report of PAPA Syndrome in Brazil

“…Curiously, two specific mutations in the same gene and domain (E250 K and E257 K) are associated to a different and specific condition, the PAMI syndrome, what requires caution in genotype versus phenotype correlation. PAPA but not PAMI has a great response to anti-IL1 therapies, and bone marrow transplantation has not yet been reported in PAPA patients [ 13 ]. Moreover, some other nonspecific clinical forms of pyoderma gangrenosum were linked to mutations in other domains of the gene and yet without a clear immunological relation.…”