Monogenic lupus with neuroregression in an infant due to rare compound heterozygous variants in C1QA gene: Case based review.

BACKGROUND: Monogenic lupus is a rare variant of systemic lupus erythematosus (SLE) that develops in patients with a single gene disorder. Early complement component deficiencies were the first forms of monogenic lupus to be described and C1Q gene mutations are one of the most common forms. C1QA complement deficiency has been reported to occur usually due to biallelic variants in C1QA gene and compound heterozygous variants in C1QA gene have rarely been reported. Majority of the monogenic lupus patients with C1Q deficiency present with mucocutaneous, renal, and musculoskeletal manifestations. Our patient is an unusual case of monogenic lupus with severe neurological manifestations along with cutaneous, haematological, and hepatic manifestations secondary to rare compound heterozygous variants in C1QA gene and anti-ribosomal P autoantibody positivity. She was treated with glucocorticoids, rituximab and fresh frozen plasma with partial neurological recovery. Thus, we present a unique case of monogenic lupus due to a rare compound heterozygous variant in C1QA gene with a brief review of literature.

Stercoral Colitis in a Patient With Pediatric-Onset Systemic Lupus Erythematosus: Case Analysis and Review of the Literature.

Systemic lupus erythematosus (SLE) is an autoantibody-related disease that affects multiple organs. Stercoral colitis (SC) is a rare type of inflammatory colitis with a high mortality rate. Here, we report the first case of pediatric-onset lupus in a case complicated by stercoral colitis. We also conducted a literature review of patients with SC under 30 years old to provide useful clues for rapid diagnosis at a young age. A 28-year-old female with a history of lupus and neuropsychiatric SLE was admitted with severe abdominal pain. She was found to have stercoral colitis during surgery. Two years later, the patient underwent Hartman's operation due to ischemia of the colon. In addition, 10 patients younger than 30 years old with a diagnosis of SC were analyzed based on clinical presentation, physical examination, laboratory exam, imaging and treatment. All cases had a favorable outcome without mortality. Stercoral colitis is a rare but lethal complication, emphasizing the importance of a multidisciplinary approach. Differential diagnosis should include stercoral colitis for patients with SLE developing unexplained sharp abdominal pain.

Clinical presentation of a neuropsychiatric lupus patient with symmetrical basal ganglia lesions containing cytotoxic oedema cores surrounded by vasogenic oedema.

Neuropsychiatric (NP) manifestations of systemic lupus erythematosus (SLE) are diverse, but involvement of basal ganglia is rare. We describe here a 28-year-old woman with NPSLE presenting aseptic meningitis accompanied by elevated interleukin-6 levels in the cerebrospinal fluid, who developed symmetrical basal ganglia lesions, containing a cytotoxic oedematous core, surrounded by vasogenic oedema upon magnetic resonance imaging. We were able to observe these lesions from a de novo appearance during the disease onset to its disappearance during immunosuppressive treatment. Reversibility upon immunosuppressive treatment indicated that autoimmune mediated mechanisms could contribute to the basal ganglia lesions in NPSLE.

Interferon-α exacerbates neuropsychiatric phenotypes in lupus-prone mice.

BACKGROUND: Neuropsychiatric systemic lupus erythaematosus (NP-SLE) is one of the major manifestations of lupus. However, the mechanisms involved in NP-SLE are still largely unknown. The abnormal activation of the type I IFN signalling pathway is involved in SLE pathogenesis and is linked to NP-SLE, but the effect of IFN-α on NP-SLE encephalopathy has not been systematically studied. METHODS: An intravenous injection of Adv-IFN-α (10 mice, 10 × 109 vp) was administered to the IFN-α-treated group, and Adv-ctrl (10 mice, 10 × 109 vp) (ViGene Biosciences, China) was administered to the control group. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in the serum, and urinary protein levels were measured with a BCA Protein Assay kit. Haematoxylin-eosin (H&E) and periodic acid-Schiff (PAS)-light green staining were used for kidney histology. The elevated plus-maze test, novelty-suppressed feeding assay, open-field test, tail suspension test, social dominance tube test, three-chamber social interaction test, step-down passive avoidance test and novelty Y-maze task were used to assess behaviour. RESULTS: In this study, we performed a series of behavioural tests to assess the neuropsychiatric phenotypes of IFN-α-treated NZB/NZW F1 mice and found that these mice developed a series of mental disorders such as anxiety-like phenotypes, depression-like phenotypes, deficits in sociability and cognitive impairments, which mimic the neuropsychiatric manifestations of NP-SLE, with a consistent onset and progression. CONCLUSIONS: Our research verified that IFN-α plays a critical role in NP-SLE and provides a comprehensive NP-SLE mouse model for dissecting the mechanisms of NP-SLE and developing novel therapies for intervention.