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High occurrence of in vitro apoptosis of lymphocytes induced by serum from systemic lupus erythematosus patients is associated with increased serum levels of anti-C1q autoantibodies

Hasan SI, Mohd Ashari NS, Mohd Daud K, Che Husin CM

Int J Rheum Dis, 2013 Aug;16(4):430-6.
PMID: 23992264 DOI: 10.1111/1756-185X.12062

BACKGROUND: The ethiopathogenesis of increased apoptosis of lymphocytes in systemic lupus erythematosus (SLE) is still incompletely understood but anti-C1q autoantibodies have been shown to induce apoptosis in lymphocytes from healthy donors and certain cell lines.
AIM: This study was undertaken to investigate the relationship between peripheral lymphocyte apoptosis and serum levels of anti-C1q autoantibodies in SLE patients.
METHODS: The sera of 124 patients with SLE involving 62 active SLE and 62 inactive SLE, fulfilling America College of Rheumatology (ACR) classification criteria for SLE (1997) were incubated with peripheral blood lymphocytes of healthy donors. The results were compared with 124 sex- and age-matched normal controls. Apoptotic lymphocytes (AL) were detected by flow cytometry using annexin V and propidium iodide binding. Anti-C1q autoantibodies were detected by an enzyme-linked immunoassay kit for all SLE patients.
RESULTS: Results demonstrated that the percentage of AL in the peripheral blood of active SLE patients was significantly higher (n = 62, 34.95 ± 12.78%) than that of the inactive SLE patients (n = 62, 30.69 ± 10.13%, P = 0.042, 95%CI = 0.16-8.36) and normal controls (n = 124, 27.92 ± 10.22%, P = 0.001, 95%CI = 3.33-10.73). The percentage of AL significantly correlated with serum levels of anti-C1q autoantibodies in the active SLE patients (r = 0.263, P = 0.039) but not in the inactive SLE patients (r = 0.170, P = 0.185).
CONCLUSION: The results of this study suggest that increased serum levels of anti-C1q autoantibodies are responsible for apoptosis and may play a pathogenic role in SLE patients, especially in active disease.
KEYWORDS: anti-C1q; apoptosis; flowcytometry; systemic lupus erythematosus
Study site: Medical outpatient clinic and medical wards, Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia

Matched MeSH terms: Lupus Erythematosus, Systemic/immunology*
Fulltext The association of the HLA class II antigens with clinical and autoantibody expression in Malaysian Chinese patients with systemic lupus erythematosus

Azizah MR, Ainoi SS, Kuak SH, Kong NCT, Normaznah Y, Rahim MN

Asian Pac J Allergy Immunol, 2001 Jun;19(2):93-100.
PMID: 11699726

The frequency of the HLA class II antigens/alleles (HLA-DR, DQ and DP) were studied in 70 Malaysian Chinese patients with systemic lupus erythematosus (SLE) to examine the contribution of these genes to disease susceptibility, their clinical expression and Immunological responses. This was done using modified PCR-RFLP technique. These samples were then compared with 66 ethnically matched controls. We found a strong association of the DQA1*0102 (p corr = 0.032, rr = 3.39), DQB1*0501 (p corr = 0.003, rr = 4.55), *0601 (p corr = 0.006, rr = 4.22) and DPB1* 0901(p corr = 0.02, rr = 4.58) with SLE. Clinically, we found a strong association of DR2 and DQA1*0301 with renal involvement and DQA1*0102 with alopecia. Immunologically, statistical analysis (Chi-square test ) showed a strong association of DQA1*0102 with anti-Ro/La antibodies while DQA1*0301 was observed to be strongly associated with antibodies to ds DNA. DQA1*0102 was found more frequently in those with a later disease onset (30 years of age or above). From these data we suggest that the HLA class II genes play a role in conferring disease susceptibility and clinical and immunological expression.
Study site: SLE clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia

Matched MeSH terms: Lupus Erythematosus, Systemic/immunology*
Fulltext Brief Report: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multiple-Dose Study to Evaluate AMG 557 in Patients With Systemic Lupus Erythematosus and Active Lupus Arthritis

Cheng LE, Amoura Z, Cheah B, Hiepe F, Sullivan BA, Zhou L, et al.

Arthritis Rheumatol, 2018 07;70(7):1071-1076.
PMID: 29513931 DOI: 10.1002/art.40479

OBJECTIVE: To evaluate the safety and potential efficacy of AMG 557, a fully human antibody directed against the inducible T cell costimulator ligand (ICOSL) in patients with systemic lupus erythematosus (SLE) with arthritis.
METHODS: In this phase Ib, randomized, double-blind, placebo-controlled study, patients received AMG 557 210 mg (n = 10) or placebo (n = 10) weekly for 3 weeks, then every other week for 10 additional doses. The corticosteroid dosage was tapered to ≤7.5 mg/day by day 85, and immunosuppressants were discontinued by day 29. Primary end points on day 169 were safety, immunogenicity, the Lupus Arthritis Response Index (LARI; defined by a reduction in the tender and swollen joint counts), ≥1-letter improvement in the musculoskeletal domain of the British Isles Lupus Assessment Group (BILAG) index, and medication discontinuation. The secondary/exploratory end points were changes in the tender and swollen joint counts, BILAG index scores (musculoskeletal, global), and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).
RESULTS: The incidence of adverse events, most of which were mild, was similar between groups. LARI responses occurred in 3 of 10 patients receiving AMG 557 and 1 of 10 patients receiving placebo (P = 0.58). More patients in the AMG 557 group achieved a ≥4-point improvement in the SLEDAI score on day 169 (7 of 10 patients) compared with the placebo group (2 of 10 patients) (P = 0.07). Patients treated with AMG 557 (versus placebo) had greater improvements from baseline in the global BILAG index scores (-36.3% versus -24.7%) and the SLEDAI score (-47.8% versus -10.7%) and in tender (-22.8% versus -13.5%) and swollen (-62.1% versus -7.8%) joint counts on day 169.
CONCLUSION: AMG 557 showed safety and potential efficacy, supporting further evaluation of the clinical efficacy of ICOSL blockade in patients with SLE.

Matched MeSH terms: Lupus Erythematosus, Systemic/immunology
Macrophage activation syndrome as an initial presentation of systemic lupus erythematosus with sensorineural hearing loss in a young male patient

Tan CL, Yahaya MH, Ahmad NS, Lim CH

BMJ Case Rep, 2020 Mar 12;13(3).
PMID: 32169986 DOI: 10.1136/bcr-2019-233330

An 18-year-old male adolescent presented with prolonged high spiking temperature, photosensitive rash, oral ulcers and reduced hearing bilaterally of recent onset. Examination revealed malar rash, vasculitis rash over bilateral palms and soles, oral and buccal ulcers, palpable posterior auricular and inguinal lymph nodes, and reduced hearing bilaterally. His further investigations noted pancytopaenia, elevated transaminases, hyperferritinaemia, low C3 and C4 levels, positive antinuclear antibody, double-stranded DNA and direct Coombs test, while bone marrow aspiration revealed active phagocytic activity suggestive of hemophagocytic syndrome. We made a diagnosis of systemic lupus erythematosus with macrophage activation syndrome. We treated him with pulse intravenous methylprednisolone and his condition improved drastically. Temperature resolved on the next day after intravenous methylprednisolone; bilateral sensorineural hearing loss improved to near-normal hearing after treatment. He remained well during follow-up with a tapering dose of prednisolone.

Matched MeSH terms: Lupus Erythematosus, Systemic/immunology