SOCS1 deficiency-crossroads of autoimmunity and autoinflammation-two case reports

Abstract

Suppressors of cytokine signaling (SOCS) proteins play a critical role in regulating immune signaling pathways. Deficiency of SOCS1 leads to various autoimmune pathologies. We present two unrelated patients with distinct clinical manifestations. Patient 1, a 16-year-old male from Guinea, presented with Evans Syndrome, musculoskeletal pain and elevated liver enzymes. Patient 2, a 6-year-old German boy, developed recurrent oral aphthous ulcers, mild inflammatory bowel disease and chronic recurrent multifocal osteomyelitis. Both patients were diagnosed with SOCS1 deficiency by genetic testing. Treatment strategies included steroids, JAK inhibition and colchicine. These cases emphasize the importance of considering SOCS1 deficiency in patients with autoimmune or autoinflammatory diseases but also in patients with unexplained elevated IgE levels. They highlight the need for further research in ongoing multicenter registries to better understand this condition.

Keywords: CNO; CRMO; SOCS1; SOCS1 deficiency; SOCS1 haploinsufficiency; autoimmunity; autoinflammation.

Figure 1

(A) Immunological features in patient 1 and patient 2 (B) STAT1 phosphorylation 1.) patient 1: elevated STAT1 phosphorylation after stimulation with IFN alpha and 2.) elevated STAT1 phosphorylation after 60 min of stimulation with IFN gamma 3.) patient 2: no elevated STAT1 phosphorylation after stimulation with IFN alpha and 4.) IFN gamma (C) 1.) interferon signature of patient 1 before start of ruxolitinib [slightly elevated, score 27,61 (<12,49)] 2.) interferon signature of patient 1 after 7 months of ruxolitinib treatment [strongly elevated, score 871,95 (<12,49)]. (D–G) Patient 2 (D) unspecific colitis with fibrin coated erosions in the rectum (E) Appendix at the age of 5 years showing irregular and progressively transformed germinal centers (BCL6 immunohistochemistry with DAB-based brown coloration, altered germinal center marked by asterisk) (F) Duodenum at the age of 8 years showing slightly elevated plasma cell densities in the lamina propria (asterisk), and slightly hyperplastic crypts (arrowhead) as signs of a minor, non-specific chronic inflammation. No villous atrophy and no intraepithelial lymphocytosis. (G) Rectum at the age of 8 years showing slightly hyperplastic mucosa on the right side, necrotic debris with neutrophils and macrophages on the left (pseudomembrane, arrowhead). Magnifications were as follows: (E) 1.4×, bar 2 mm; (F/G) 40×, bar 50 µm. Histological sections were digitized with the Aperio slide scanner (Leica, Nussloch, Germany), with an original magnification of 40× and an original resolution 0.253 µm per pixel. (H/I)Patient 2: Focal T2w signal alterations (arrowheads) in the distal third of the right femur (H), and in the ischium on the left (I) indicating lesions suggestive of CRMO.