SOCS1 Insufficiency - a Rare Inborn Error of Immunity

Jack Cush, MD

Mar 03, 2025 9:00 am

Lancet Rheumatology has published a population study of the rare suppressor of cytokine signalling 1 (SOCS1) insufficiency - an inborn error of immunity affecting the negative regulation of cytokine and growth factor signalling.

It was first discovered in 2020. SOCS1 insufficiency manifests allergic and rheumatological features and manifestations with markedly upregulated JAK signalling.

This multinational study identified patient cohorts: the European Society for Immunodeficiencies (ESID) registry and the UK Biobank. Patients were included if they had functionally validated SOCS1 variants. Looking at both the ESID and UK Biobank registries they found:

Most were female (58% and 56% respectively)
Median age was 28 years (range 2–85) and 72 years (range 57–86).
ESID: 27 different monoallelic SOCS1 variants. UK Biobank identified 52 participants with high-impact SOCS1 variants
93% in the ESID registry cohort were symptomatic and
- Symptoms were allergic (50%), inflammatory gastrointestinal (36%), skin (29%) or rheumatic (37%)
- Lab findings of autoimmune cytopenia (39%), and lymphoproliferation (37%)
- Rheumatological manifestations included features of systemic lupus erythematosus, Sjögren's disease, and rheumatoid arthritis, with typical autoantibodies
While many of the rheumatic drugs were used, treatment with JAK inhibitors was promising and showed good/very good results in 12/13 (92%) in the ESID registry.

Authors recommend that genetic testing for SOCS1 insufficiency may be considered in all patients with a combination of allergic, inflammatory and rheumatologic disease. Such patients may need to be comanaged by rheumatologists, allergists, and immunologists.

Clinical manifestations, disease penetrance, and treatment in individuals with SOCS1 insufficiency: a registry-based and population-based study