Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease with both autoimmune and autoinflammatory components. Recently, familial cases of systemic-onset JIA have been attributed to mutations in LACC1/FAMIN. We describe three affected siblings from a Moroccan consanguineous family with an early-onset chronic, symmetric and erosive arthritis previously diagnosed as rheumatoid factor (RF)-negative polyarticular JIA. Autozygosity mapping identified four homozygous regions shared by all patients, located in chromosomes 3, 6 (n:2) and 13, containing over 330 genes. Subsequent whole exome sequencing identified two potential candidate variants within these regions (in FARS2 and LACC1/FAMIN). Genotyping of a cohort of healthy Moroccan individuals (n: 352) and bioinformatics analyses finally supported the frameshift c.128_129delGT mutation in the LACC1/FAMIN gene, leading to a truncated protein (p.Cys43Tyrfs*6), as the most probable causative gene defect. Additional targeted sequencing studies performed in patients with systemic-onset JIA (n:23) and RF-negative polyarticular JIA (n: 44) revealed no pathogenic LACC1/FAMIN mutations. Our findings support the homozygous genotype in the LACC1/FAMIN gene as the defect underlying the family here described with a recessively inherited severe inflammatory joint disease. Our evidences provide further support to the involvement of LACC1/FAMIN deficiency in different types of JIA in addition to the initially described systemic-onset JIA.This work has been partially funded by: CERCA Programme/Generalitat de Catalunya (JIA, XE, SO), the PERIS program of the Generalitat de Catalunya grant SLT002/16/00310 (RR), the Spanish Ministry of Economy and Competitiveness co-financed by European Regional Development Fund (ERDF) grant SAF2015-68472-C2-1-R (JIA), the Instituto de Salud Carlos III/Transnational Research Projects on Rare Diseases (JIA) grant AC15/00027, the Spanish Society of Pediatric Rheumatology (JIA), the Secretaria d’Universitats i Recerca del Departament d’Economia grant 2009-SGR-1502 (XE) and the European Union Seventh Framework Programme (FP7/2007-2013) grant agreement no. 262055 (XE)

Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease with both autoimmune and autoinflammatory components. Recently, familial cases of systemic-onset JIA have been attributed to mutations in LACC1/FAMIN. We describe three affected siblings from a Moroccan consanguineous family with an early-onset chronic, symmetric and erosive arthritis previously diagnosed as rheumatoid factor (RF)-negative polyarticular JIA. Autozygosity mapping identified four homozygous regions shared by all patients, located in chromosomes 3, 6 (n:2) and 13, containing over 330 genes. Subsequent whole exome sequencing identified two potential candidate variants within these regions (in FARS2 and LACC1/FAMIN). Genotyping of a cohort of healthy Moroccan individuals (n: 352) and bioinformatics analyses finally supported the frameshift c.128_129delGT mutation in the LACC1/FAMIN gene, leading to a truncated protein (p.Cys43Tyrfs*6), as the most probable causative gene defect. Additional targeted sequencing studies performed in patients with systemic-onset JIA (n:23) and RF-negative polyarticular JIA (n: 44) revealed no pathogenic LACC1/FAMIN mutations. Our findings support the homozygous genotype in the LACC1/FAMIN gene as the defect underlying the family here described with a recessively inherited severe inflammatory joint disease. Our evidences provide further support to the involvement of LACC1/FAMIN deficiency in different types of JIA in addition to the initially described systemic-onset JIA.This work has been partially funded by: CERCA Programme/Generalitat de Catalunya (JIA, XE, SO), the PERIS program of the Generalitat de Catalunya grant SLT002/16/00310 (RR), the Spanish Ministry of Economy and Competitiveness co-financed by European Regional Development Fund (ERDF) grant SAF2015-68472-C2-1-R (JIA), the Instituto de Salud Carlos III/Transnational Research Projects on Rare Diseases (JIA) grant AC15/00027, the Spanish Society of Pediatric Rheumatology (JIA), the Secretaria d’Universitats i Recerca del Departament d’Economia grant 2009-SGR-1502 (XE) and the European Union Seventh Framework Programme (FP7/2007-2013) grant agreement no. 262055 (XE)

Cellular Immunity of SARS-CoV-2 in the Borriana COVID-19 Cohort: A Nested Case–Control Study

Our goal was to determine the cellular immune response (CIR) in a sample of the Borriana COVID-19 cohort (Spain) to identify associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case–control study using a randomly selected sample of 225 individuals aged 18 and older, including 36 individuals naïve to the SARS-CoV-2 infection and 189 infected patients. We employed flow-cytometry–based immunoassays for intracellular cytokine staining, using Wuhan and BA.2 antigens, and chemiluminescence microparticle immunoassay to detect SARS-CoV-2 antibodies. Logistic regression models were applied. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3%, respectively. No difference in CIR was found between naïve and infected patients. Patients who experienced sequelae exhibited a higher CIR than those without. A positive correlation was observed between TCR and anti-spike IgG levels. Factors positively associated with the TCR included blood group A, number of SARS-CoV-2 vaccine doses received, and anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and blood group B. These findings contribute valuable insights into the nuanced immune landscape shaped by SARS-CoV-2 infection and vaccination

ABO Blood Groups and the Incidence of Complications in COVID-19 Patients: A Population-Based Prospective Cohort Study

After a COVID-19 outbreak in the Falles festival of Borriana (Spain) during March 2020, a cohort of patients were followed until October 2020 to estimate complications post-COVID-19, considering ABO blood groups (ABO). From 536 laboratory-confirmed cases, 483 completed the study (90.1%) carried by the Public Health Center of Castelló and the Emergency and Microbiology and Clinical Analysis of Hospital de la Plana Vila-real. The study included ABO determination and telephone interviews of patients. The participants had a mean age of 37.2 ± 17.1 years, 300 females (62.1%). ABO were O (41.4%), A (45.5%), B (9.1%), and AB (3.9%). We found no difference in the incidence of COVID-19 infections. A total of 159 (32.9%) patients reported one or more post-COVID-19 complications with divergent incidences after adjustment: O (32.3%), A (32.6%), B (54.1%), and AB (27.6%); B groups had more complications post-COVID-19 when compared with O group (adjusted relative risk [aRR] 95% confidence interval [CI] 1.68, 95% CI 1.24–2.27), and symptoms of fatigue (1.79, 95% CI 1.08–2.95), myalgia (2.06, 95% CI 1.10–3.84), headache (2.61, 95% CI 1.58–4.31), and disorder of vision (4.26 95% CI 1.33–13.60). In conclusion, we observed significant differences in post-COVID-19 complications by ABO, with a higher incidence in B group. Additional research is justified to confirm our results

Persistence of Anti-SARS-CoV-2 Antibodies Six Months after Infection in an Outbreak with Five Hundred COVID-19 Cases in Borriana (Spain): A Prospective Cohort Study

In March 2020, several mass gathering events were related to the Falles festival in Borriana (Spain), resulting in a 536 laboratory-confirmed COVID-19 cases outbreak among participants. This article estimates anti-SARS-CoV-2 antibodies persistence six months after and factors associated with antibody response. A prospective population-based cohort study was carried out by the Public Health Centre of Castellon and the Emergency and Clinical Analysis and Microbiology Services of Hospital de la Plana in Vila-real. In October 2020, a seroepidemiologic study was used to estimate the persistence of anti-SARS-CoV-2 antibodies against nucleocapsid protein (N) by an electrochemiluminescence immunoassay (ECLIA) was implemented. We enrolled 484 (90.2%) of the 536 members of the initial outbreak cohort and detected persistent antibodies in 479 (99%) without reinfection episodes. Five participants had a negative antibody test. Factors associated with a negative result were a lower body mass index (BMI), and less contact with other COVID-19 cases. Among the 469 participants with two ECLIA tests, 96 (20.5%) had an increase of antibodies and 373 (79.5%) a decline. Increased antibodies were associated with older age, higher BMI, more severe illness, and low current smokers. Our results show that after a COVID-19 infection, a high proportion of cases maintain detectable anti-SARS-CoV-2 antibodies