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Objective: To characterize the demographic, genetic, clinical, and serological features of patients with anti-3‑hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotizing myopathy (IMNM) in a region of northern Spain., Methods: Study of all patients diagnosed with anti-HMGCR IMNM during a 5-year period at a reference hospital in northern Spain. Besides clinical and laboratory data, we analyzed the genetic influence of HLA genes and the rs4149056 (c.521T>C) single nucleotide polymorphism (SNP) in the SLCO1B1 gene., Results: 8 patients (5 women, 3 men) with a mean ± SD age of 64.9 ± 7.3 years, fulfilled the criteria for anti-HMGCR IMNM. The incidence rate was 0.6 per 100.000 person-years and the prevalence 3 per 100.000 population. All patients had been exposed to statins. All of them had predominant lower limb proximal and symmetric muscle weakness that was severe in 2 and had elevated serum CK levels with a median [IQR] of 4488 [2538-9194] IU/L. Serum 25‑hydroxy vitamin D levels were decreased in all patients in whom it was determined. The 3 patients with a previous diagnosis of hypothyroidism had abnormal levels of TSH at the time of diagnosis. All patients experienced improvement with different schemes of immunosuppressive therapy. Noteworthy, 7 of 8 patients carried the HLA-DRB1*11 allele. The frequency of the rs4149056 C allele in the SLCO1B1 gene (12.5%) was similar to that of the general population., Conclusion: In northern Spain, anti-HMGCR IMNM preferentially affects people over 50 years of age who are carriers of the HLA-DRB1*11 allele and take statins. Both low vitamin D levels and hypothyroidism may play a potential predisposing role in the development of this disease., (Copyright © 2022. Published by Elsevier B.V.)

Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 levels as a potential biomarker of ASSD susceptibility and for the differential diagnosis between patients with ILD associated with ASSD (ASSD-ILD +) and idiopathic pulmonary fibrosis (IPF). 168 ASSD patients (149 ASSD-ILD +), 174 IPF patients and 523 healthy controls were genotyped for MUC1 rs4072037 T > C. Serum KL-6 levels were determined in a subgroup of individuals. A significant increase of MUC1 rs4072037 CC genotype and C allele frequencies was observed in ASSD patients compared to healthy controls. Likewise, MUC1 rs4072037 TC and CC genotypes and C allele frequencies were significantly different between ASSD-ILD+ and IPF patients. Additionally, serum KL-6 levels were significantly higher in ASSD patients compared to healthy controls. Nevertheless, no differences in serum KL-6 levels were found between ASSD-ILD+ and IPF patients. Our results suggest that the presence of MUC1 rs4072037 C allele increases the risk of ASSD and it could be a useful genetic biomarker for the differential diagnosis between ASSD-ILD+ and IPF patients., (© 2021. The Author(s).)

Objective: To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD)., Methods: We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing., Results: A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P=1.56E-09, odds ratio-OR [95% confidence interval-CI]=2.54 [1.84-3.50] and 21.4% versus 5.5%, P=18.95E-18, OR [95% CI]=4.73 [3.18-7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P=0.0003, OR [95% CI]=0.48 [0.31-0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P=0.001, OR [95% CI]=2.54 [1.39-4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed., Conclusions: Our results support the association of the HLA complex with the susceptibility to ASSD., (Copyright © 2020 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)