complement component C1r/C1s deficiency

Complement component C1r/C1s deficiency is a condition characterized by an inability to produce functional C1r or C1s proteins due to an underlying defect. This deficiency impacts the immune system and is associated with the early development of severe systemic lupus erythematosus in approximately 60% of affected individuals. In addition, patients frequently experience sinopulmonary infections, often caused by Streptococcus pneumoniae. The precise prevalence is not well established, and the underlying genetic basis is still under investigation.

Patients with complement component C1r/C1s deficiency may develop severe systemic lupus erythematosus at an early age and are prone to recurrent sinopulmonary infections, particularly with Streptococcus pneumoniae. These features often drive the initial clinical concern and prompt a medical evaluation. Not all individuals experience all features, and severity varies considerably. The clinical picture underscores an immune dysregulation that can lead to both autoimmune manifestations and increased susceptibility to infections.

The precise genetic basis for complement component C1r/C1s deficiency is still under investigation, although the condition results from a defect that impairs the production of functional C1r or C1s proteins. It is inherited in an autosomal recessive pattern, meaning that an affected individual receives two defective copies of the gene, one from each parent. This inheritance pattern implies that both parents are likely to be carriers, and genetic counseling is recommended to help families understand potential recurrence risks and options for family planning.

Currently, management of complement component C1r/C1s deficiency focuses on supportive care and symptom management. Treatment is tailored to the individual and typically involves a multidisciplinary team to address autoimmune complications and prevent or manage infections. In the absence of targeted therapies, strategies may include immunomodulatory treatments, infection prophylaxis, and routine monitoring. Patients should discuss treatment options with their healthcare team to determine which approaches are most appropriate for their situation and may also consider genetic counseling for additional guidance.

Outcomes for individuals with complement component C1r/C1s deficiency can vary widely, with some patients experiencing significant autoimmune challenges early in life while others have a milder course. With current standards of care and appropriate management of symptoms, many individuals are able to achieve an improved quality of life. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with immunology and rheumatology specialists, as well as consider genetic counseling, to obtain personalized guidance and support.