Defect in Genes May Trigger Neuropsychiatric Symptoms in Lupus Patients, Study Says

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

Share this article:

Share article via email
black lupus risk

A defect in the C1q genes commonly associated with systemic lupus erythematosus (SLE) may promote serious neuropsychiatric symptoms in those with the disease, a case study suggests.

The research, “C1q Deficiency and Neuropsychiatric Systemic Lupus Erythematosus,” was published in the journal Frontiers in Immunology.

C1q deficiency is a genetic disease caused by mutations, or defects, in three C1q genes – C1qA, C1qB, and C1qC. It is linked to a defective part of our immune system, the complement system, which plays an important role in our defense against certain pathogens.

Previous research showed a strong connection between C1q deficiency and SLE. In fact, C1q mutations are the most important genetic factor predisposing people to the disease, studies showed.

The most common manifestations of C1q deficiency are skin and kidney problems. In addition, it is estimated that 20% of C1q-deficient patients have severe neuropsychiatric symptoms.

The case study involved a 24-year-old C1q-deficient Dutch man who had a mutation associated with neuropsychiatric SLE. Researchers dubbed the mutation low-molecular weight (LMW) C1q.

The patient had a cheek rash and discoid lupus, or lumps on his skin, that caused mild scarring and atrophy.

Magnetic resonance imaging also showed alterations in the patient’s brain. They included multifocal diffuse gray matter hyperintensities in the frontotemporal right lobe, and high-intensity areas in several parts of the right frontal and parietal lobes.

Researchers reviewed 15 articles about C1q deficiency in SLE to try to find a link between the patients’ C1q and their neuropsychiatric symptoms.

“Among all C1q-deficient patients with NP [neuropsychiatric]-SLE described so far in the literature, seizures were the most frequent neuropsychiatric symptom presented (10 patients; 67%),” they wrote.

Five patients, or 33%, had “severe non-specific NP symptoms characterized by encephalopathy and difficulties to walk associated with cerebral infarcts and thought to be related with a cerebral vasculitis,” the team wrote. “Transverse myelitis and psychosis were also present in two patients (13%). Neuroimaging of the brain showed a more frequent finding affection of basal ganglia (calcification or ischemic lesions) in 40% of the cases, followed by cerebral vasculitis (27%) and brain atrophy (20%).

“A defective CP [complement pathway], because of non-functional C1q, does not protect against NP involvement in SLE,” the team concluded, adding: “The absence of C1q and, subsequently, some of its biological functions, may be associated with more severe NP-SLE.”