Abstract
C1q deficiency is a rare immunodeficiency, which is strongly associated with the development of systemic lupus erythematosus (SLE). A mutation in one of the C1q genes can either lead to complete deficiency or to low C1q levels with C1q polypeptide in the form of low-molecular weight (LMW) C1q. Patients with C1q deficiency mainly present with cutaneous and renal involvement. Although less frequent, neuropsychiatric (NP) involvement has also been reported in 20% of the C1q-deficient patients. This involvement appears to be absent in other deficiencies of early components of the complement classical pathway (CP) (C1r/C1s, C2, or C4 deficiencies). We describe a new case with C1q deficiency with a homozygous G34R mutation in C1qC-producing LMW-C1q presenting with a severe SLE flare with NP involvement. The serum of this patient contained very low levels of a LMW variant of C1q polypeptides. Cell lysates contained the three chains of C1q, but no intact C1q was detected, consistent with the hypothesis of the existence of a LMW-C1q. Furthermore, we provide a literature overview of NP-SLE in C1q deficiency and hypothesize about the potential role of C1q in the pathogenesis of NP involvement in these patients. The onset of NP-SLE in C1q-deficient individuals is more severe when compared with complement competent NP-SLE patients. An important number of cases present with seizures and the most frequent findings in neuroimaging are changes in basal ganglia and cerebral vasculitis. A defective CP, because of non-functional C1q, does not protect against NP involvement in SLE. The absence of C1q and, subsequently, some of its biological functions may be associated with more severe NP-SLE.
Highlights
C1q deficiency is a rare autosomal recessive-inherited defect of the complement system caused by mutations occurring in one of the three C1q genes (C1qA; C1qB; and C1qC) [1]
The present study investigated an extremely rare case of C1q deficiency due to non-functional LWM-C1q associated with a severe clinical phenotype presenting with membranous lupus nephritis and a mixed inflammatory and ischemic neuropsychiatric systemic lupus erythematosus (NP-systemic lupus erythematosus (SLE))
The production of C1q by neuronal cells was reported to lead to opsonization of synapses in the developing postnatal central nervous system (CNS), which are eliminated by microglia [27]
Summary
C1q deficiency is a rare autosomal recessive-inherited defect of the complement system caused by mutations occurring in one of the three C1q genes (C1qA; C1qB; and C1qC) [1]. To exclude the possibility that next to C1q deficient, the patients sample would be deficient for C1r or C1s, we performed assays to measure activation of the CP of the patient serum by reconstitution of purified C1q. This is compatible with a C1q deficiency, but to exclude that next to C1q other factors would be deficient in the patient, we performed a reconstitution assay where we add purified C1q to the serum of the patient and analyze C4 deposition.
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