Complement C1s deficiency in a male Caucasian patient with systemic lupus erythematosus: a case report

Area of Science:

• Immunology
• Genetics

Background:

• Deficiencies in early complement components of the classical pathway (CP) are linked to systemic lupus erythematosus (SLE) and severe infections.
• Complete C1s deficiency is exceptionally rare, with only nine cases previously reported.

Observation:

• A 34-year-old male presented with recurrent severe infections and adult-onset SLE, including class IV proliferative lupus nephritis.
• Complement screening revealed undetectable C1s with low C1r/C1q, normal C3, and elevated C4/C2, alongside normal alternative pathway function.
• Renal biopsy showed lupus nephritis with C1q deposition, and functional assays confirmed absent complement activity restored by C1s addition.

Findings:

• Whole genome sequencing identified two novel truncating nonsense mutations in the C1S gene, confirming compound heterozygote C1s deficiency.
• The patient's clinical presentation of recurrent infections and SLE is consistent with classical pathway deficiency.
• The patient showed a positive response to rituximab treatment, similar to a previously reported C1s deficiency case.

Implications:

• This case expands the known spectrum of C1s deficiency and its genetic basis.
• It underscores the critical role of the classical complement pathway in SLE pathogenesis.
• Further research is needed to fully elucidate the CP's role in SLE and optimize treatment strategies for complement deficiencies.