C1q monogenic lupus: a case series and review

Monogenic systemic lupus erythematosus (SLE) is caused by a single gene mutation. C1q deficiency is a rare but well-documented form of monogenic SLE, characterized by unique clinical and laboratory indicators that guide diagnosis and treatment. We aimed to describe four cases of C1q monogenic lupus.

This retrospective, single-centre observational study reviews the clinical and serological profiles and outcomes of four cases of C1q Monogenic Lupus diagnosed at our centre. The study was approved by the Institutional Ethics Committee at the Institute of Postgraduate Medical Education and Research (IPGMER), Kolkata-700020 (Memo No. IPGME&R/IEC/2025/0020).

We describe four cases of C1Q monogenic lupus identified by whole exome sequencing. All patients exhibited mucocutaneous involvement, discoid lupus erythematosus, inflammatory polyarthritis, normal serum complements C3 and C4, coarse-speckled Antinuclear antibody positivity and antibodies to ribonucleoprotein. Unique features identified include brain parenchymal calcification in one case, chronic subdural haemorrhage in two cases, infection complicated by macrophage activation syndrome in two cases and myositis in one case. Patients were treated with conventional immunosuppressive therapy (glucocorticoids, mycophenolate, cyclophosphamide) and Fresh Frozen Plasma. Our findings were compared with existing literature on C1q deficiency, noting frequent presentations with mucocutaneous and musculoskeletal manifestations, normal C3 and C4 levels and absence of anti-dsDNA antibodies.

C1Q Monogenic SLE should be suspected in juvenile SLE patients presenting at under 10 years, with a family history of consanguinity, predominant mucocutaneous manifestations, a history of recurrent infection, normal serum complements and absence of C1q staining in direct immunofluorescence of renal biopsy. In our series, autoimmune manifestations responded well to immunosuppressive therapy.