Biological and glucocorticoids treatment impair the medium-term immunogenicity to SARS-CoV-2 mRNA vaccines in autoimmune inflammatory rheumatic diseases.

BACKGROUND: This study aims to assess the sustained immunological response to the SARS-CoV-2 vaccine in patients with autoimmune inflammatory rheumatic diseases (AIRD) undergoing different treatment regimens. METHODS: We conducted a prospective observational study involving 157 AIRD patients without prior COVID-19 infection. Treatment regimens included non-treatment or glucocorticoid-only (not-treated/GCs), non-biological drugs, biological therapy, and JAK inhibitors. All participants completed the two-dose vaccine schedule, and 110 of them received an additional booster dose. Serum samples were collected approximately 3-6 months after the second and third vaccine doses to measure antibodies against the Spike protein (antiS-AB) and neutralizing antibodies (nAB) targeting six SARS-CoV-2 variants. RESULTS: Following the third dose, all patients exhibited a significant increase in antiS-AB (FC = 15, p < 0.0001). Patients under biological therapy had lower titres compared to the non-biological (66% decrease, p = 0.038) and the not-treated/GCs group (62% decrease, p = 0.0132), with the latter persisting after the booster dose (86% decrease, p = 0.0027). GC use was associated with lower antiS-AB levels in the biological group (87% decrease, p = 0.0124), although not statistically significant after confounders adjustment. nABs showed the highest positivity rates for the wild-type strain before (50%) and after the booster dose (93%), while the Omicron variant exhibited the lowest rates (11% and 55%, respectively). All variants demonstrated similar positivity patterns and good concordance with antiS-AB (AUCs from 0.896 to 0.997). CONCLUSIONS: The SARS-CoV-2 vaccine booster strategy effectively elicited a sustained antibody immune response in AIRD patients. However, patients under biological therapies exhibited a reduced response to the booster dose, particularly when combined with GCs.

Contribution of LILRB1 polymorphism and HLA-DRB1-shared epitope to rheumatoid arthritis

Objectives: The LILRB1 gene has recently been associated with rheumatoid arthritis (RA)susceptibility in HLA-DRB1-shared epitope (SE) negative Japanese individuals. Since the contribution of the LILRB1 polymorphism to RA susceptibility may vary among ethnic populations, we examined this association in a group of Caucasian patients. The frequency ofLILRB1 alleles was also determined in patients according to the presence of DRB1-SE. Methods: Samples from 103 RA patients and 107 healthy controls were randomly collected. Polymorphism of the LILRB1 gene was analyzed by sequencing with primers that amplifiedintron 3 and exon 4.Results: The frequencies of LILRB1 alleles in RA patients did not differ from those of controls. However, when patients and controls were grouped according to SE, the PE-01/01 genotype was less frequent in negative-SE patients than in controls. Whereas SE is associated with higher anti-CCP antibody levels, as expected, the production of anti-CCP antibodies was lower in negative-SE patients with PE-01/01 genotype. Moreover, radiographic damage in hand and feet of SE-negative PE-01/01 patients was less severe than in patients with other genotypes. Conclusions: The participation of this LILRB1 polymorphism in the RA pathogenesis of this Caucasian cohort differed from that reported in a Japanese sample. Our findings suggest that the LILRB1-PE-01/01 genotype could exert a protective role in RA susceptibility and disease severity in the absence of SE (AU)

Objetivos: El gen LILRB1 se ha asociado a la susceptibilidad a desarrollar artritis reumatoide(AR) en aquellos individuos japoneses negativos para el epítopo compartido del HLA-DRB1.Dado que la contribución del polimorfismo en LILRB1 a la susceptibilidad a desarrollar artritis reumatoide puede variar según las distintas etnias, hemos examinado esta asociación con la artritis reumatoide en un grupo de pacientes caucásicos. La frecuencia de los alelosLILRB1 fue también determinada en los pacientes clasificados según la presencia del epítopo compartido. Métodos: Se recogieron al azar muestras de 103 pacientes de AR y 107 controles sanos. El polimorfismo en el gen LILRB1 se analizó con cebadores que amplificaban el intrón 3 y elexón 4.Resultados: Las frecuencias diploides de los alelos de LILRB1 en los pacientes de artritis reumatoide no diferían de la de los controles. Sin embargo, cuando los pacientes y controles se agruparon según la presencia del epítopo compartido, la frecuencia del genotipo PE-01/01fue menor en los pacientes con epítopo compartido negativo que en controles con epítopo compartido negativo. Mientras que el epítopo compartido se asoció con niveles altos de anticuerpos anti-CCP, la producción de anticuerpos anti-CCP fue menor en pacientes con epítopo compartido negativo y genotipo PE-01/01. Además, el daño radiográfico en manos y pies en pacientes con epítopo compartido negativo y genotipo PE-01/01 fue menos severa que en pacientes con otros genotipos. Conclusiones: La participación del polimorfismo del LILRB1 en la fisiopatogenia de la AR en esta cohorte de pacientes Caucásicos difiere de la publicada en los pacientes japoneses. Nuestros resultados sugieren que el genotipo LILRB1-PE-01/01 puede ejercer un papel en la susceptibilidad de la AR y en la severidad de la misma en ausencia del epítopo compartido (AU)