Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced agranulocytosis is important for clinical management. We performed a genome-wide association study (GWAS) involving 20 patients with ATD-induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single-nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD-induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8-103.7; P = 1.3 × 10(-24)) and replication (OR = 37; 95% CI = 3.7-367.4; P = 9.6 × 10(-7)). HLA-B*38:02:01 was in complete linkage disequilibrium with rs185386680. High-resolution HLA typing confirmed that HLA-B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)-induced agranulocytosis (OR = 265.5; 95% CI = 27.9-2528.0; P = 2.5 × 10(-14)), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA-B*38:02:01 in predicting CMZ/MMI-induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.

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BackgroundWhether COVID-19 infection worsens SLE activity is uncertain.ObjectivesTo study the effect of COVID-19 infection on disease flares and herpes zoster (HZ) reactivation in patients with systemic lupus erythematosus (SLE).MethodsPatients who fulfilled the ACR or SLICC criteria for SLE and were followed in our rheumatology clinics were retrospectively studied. We identified patients who had documented COVID-19 infection (Omicron and its variants) between February and November 2022 and a group of SLE controls who did not have COVID-19 infection randomly matched for age, sex and the time period of COVID-19 infection in a 1:2 ratio. The primary outcomes of interest were SLE flares (clinical or serological) and the occurrence of HZ infection within 90 days of COVID-19 infection. SLE flares were assessed by the SELENA flare instruments, with modifications (mild/moderate or severe). HZ infection was a clinical diagnosis based on history and physical signs by attending physicians. The rates of SLE flares and HZ reactivation were compared between COVID-infected SLE patients and controls.Results91 SLE patients with COVID-19 infection (age 48.6±14.0 years; 95.6% women; SLE duration 14.2±8.3 years; 53% history of lupus nephritis) and 182 SLE controls not infected by COVID-19 (age 48.7±13.8 years; 95.6% women; SLE duration 15.2±9.0 years) were studied. Eleven of 90 (12.2%) COVID-infected patients had serious manifestations (oxygen requirement, use of mechanical ventilator, lung infiltrates on imaging studies or admission to the intensive care unit). Patients with mild COVID-19 infection were treated symptomatically or oral anti-viral agents whereas those with serious COVID-19 infection was treated with intravenous remdesivir, dexamethasone and/or biologic/targeted agents. One (1.1%) of our patients died and 7(7.7%) patients developed severe complications. Within 90 days of COVID-19 infection, 14 (15.4%) patients developed mild/moderate SLE flares and 2 (2.2%) patients had severe SLE flares. The incidence of SLE flares in COVID-19-infected patients was significantly higher than those without (17.6% vs 5.5%; p=0.001). The changes in anti-dsDNA and complement C3 levels, however, were not significantly different between the two groups. Among COVID-19 infected SLE patients, those with clinical SLE flares had significantly lower C3 values (p=0.004) but non-significantly higher anti-dsDNA titer (p=0.32) before COVID-19 infection than those without SLE flares. HZ reactivation occurred in 2 patients (2.2%) with COVID-19 infection, which was numerically higher than those not infected by COVID-19 (2 patients, 1.1%; p=0.48). No particular risk factors were identified for HZ reactivation after COVID-19 infection.ConclusionIn this retrospective case-control study, clinical flares within 90 days were significantly more common in patients infected with COVID-19 than age and gender matched non-infected SLE controls. SLE patients with lower C3 levels were more likely to flare after COVID-19 infection. HZ reactivation occurred at a numerically higher rate after COVID-19 infection in SLE patients than controls. The results from our study support the hypothesis for a viral trigger for disease exacerbation in SLE.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.