title: C1q Deficiency and Neuropsychiatric Systemic Lupus Erythematosus.
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.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Rosanne A
authors.initials: RA
authors.lastname: van Schaarenburg
authors.affiliation: Department of Rheumatology, Leiden University Medical Center , Leiden , Netherlands.
authors.forename: César
authors.initials: C
authors.lastname: Magro-Checa
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Bakker
authors.affiliation: Department of Nephrology, Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Y K Onno
authors.initials: YK
authors.lastname: Teng
authors.affiliation: Department of Pathology, Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Bajema
authors.affiliation: Department of Rheumatology, Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Tom W
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Rheumatology, Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Gerda M
authors.initials: GM
authors.lastname: Steup-Beekman
authors.affiliation: Department of Rheumatology, Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Leendert A
authors.initials: LA
authors.lastname: Trouw
keywords: C1q deficiency; complement; low molecular weight C1q; mutation; neuropsychiatric systemic lupus erythematosus