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.

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.…”