Oscar Correa-Jiménez

Background: Adalimumab, a monoclonal antibody targeting tumor necrosis factor α, treats autoimmune diseases but induces antidrug antibodies in 30% to 60% of patients, reducing its efficacy. Objective: This study aims to investigate molecular mimicry as a mechanism behind this immunogenicity, where bacterial immunoglobulin domains structurally resemble adalimumab’s light chain, triggering immune responses. Methods: Using PSI-BLASTp (National Center for Biotechnology Information) and PRALINE (Center for Integrative Bioinformatics), there are 40 bacterial antigens homologous to adalimumab, with 8 clinically relevant strains. Results: Structural analysis revealed 94% amino acid identity between the immunoglobulin domain of Escherichia coli strain B1 and adalimumab’s light chain, and 89.67% similarity with Corynebacterium pyruviciproducens . Root mean square deviation values confirmed strong structural homology. Additionally, 5 cross-reactive B-cell epitopes were predicted, suggesting overlapping surfaces that may promote immune cross-reactivity and antidrug antibody development. Conclusions: This study represents a first step toward identifying a potential microbial factor driving antiadalimumab antibody formation. The predicted cross-reactive regions provide specific candidates for further in vitro validation to confirm molecular mimicry and refine epitope mapping. Understanding these mechanisms may ultimately inform the design of less immunogenic biologics and guide clinical strategies to predict and prevent antidrug antibody formation.

Schizophrenia is a complex disorder influenced by genetic, neurobiological, and environmental factors, with increasing evidence implicating immune dysregulation. This study examined potential molecular mimicry between autoantigens associated with schizophrenia and proteins from Toxoplasma gondii, a parasite previously linked to the disorder. Amino acid sequences of schizophrenia-related autoantigens were retrieved from databases (AAgAtlas, PubMed), and homologous sequences were searched within the T. gondii proteome. Sequence identity was evaluated, and conserved B-cell epitopes were predicted using three-dimensional structures from the Protein Data Bank or models generated in Swiss-Model, followed by epitope mapping with ElliPro. Five autoantigens—gamma-enolase (ENO2), thyroid peroxidase (TPO), glutamic acid decarboxylase 65 kDa isoform (GAD65), serine/threonine-protein kinase 2 (VRK2), and dihydropyrimidine dehydrogenase [NADP(+)] (DPYD)—showed similarities with T. gondii proteins. Among them, enolase exhibited the highest homology, with identities up to 65%. These findings provide preliminary evidence of shared antigenic features between the parasite and schizophrenia-related autoantigens. Such mimicry could contribute to disease mechanisms by triggering autoimmune responses in genetically susceptible individuals, supporting the hypothesis that T. gondii infection may influence schizophrenia pathogenesis. Nonetheless, the results are based exclusively on in silico analyses, and experimental validation will be required to confirm potential cross-reactivity.

Human proteinase 3 (hPR3) is a lysosomal enzyme of the serine protease type. In autoimmune vasculitis, autoantibodies to hPR3 appear to have a role in the inception of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), where this protein is the main autoantigen. Indeed, patients with antibodies against hPR3 have more severe symptoms, relapses, and resistance to immunosuppressive therapies, supporting an important role for this autoantigen in the pathophysiology and severity of AAV. In this review, we describe what is known about the role of hPR3 in pathophysiology, diagnosis of AAV, and some perspectives on its treatment.

Background: Although some reports indicate ocular involvement in Inborn Errors of Immunity (IEI) patients, the characteristics of this association remain unclear. Increased awareness can facilitate early diagnosis and prevention of visual complications. Objective: To determine the prevalence and characterize ophthalmological manifestations in patients with IEI. Methods: A systematic literature search was performed across Embase, PubMed, and Lilacs. Observational studies with at least 10 IEI patients exhibiting ophthalmological manifestations were reviewed. A meta-analysis using a random effects model, weighted proportion, and 95% confidence intervals were reported as appropriate. Results: Sixty-two articles out of the 6,884 studies were included. The pooled prevalence of ocular manifestations in IEI patients was 54% (95%CI = 39–69), with a mean age of 11.1 ± 7.8 years and male predominance. Regarding the type of IEI with ocular involvement, the most frequently affected group was the Combined immunodeficiencies with associated or syndromic features (82%, 95%CI = 66–91), followed by the diseases of immune dysregulation (73%, 95%CI = 27–95), auto-inflammatory disorders (48%, 95%CI = 10–88), and congenital defects of phagocytes (39%, 95%CI = 11–76). Europe had the highest prevalence of patients with ocular manifestations (68%, 95%CI = 32–90). The most common ocular manifestations observed in IEI patients were those affecting ocular mobility, followed by those that involved the anterior segment, posterior segment, eyelids, and adnexal structures. Conclusions: These results highlight a significant burden of ocular involvement in IEI patients, mainly during childhood and associated with amblyogenic factors. Therefore, ophthalmologists, pediatricians, and immunologists must be involved in early detection to prevent ocular complications and overall well-being.

Autoimmune responses are characterized by the development of antibodies and the activation of T lymphocytes against self-antigens. This leads to an effector immuneresponse against tissues expressing antigens, which are later recognized by the host immune system.Host antigens attacked by antibodies are called “autoantigens” and are of different kinds, including receptors, enzymes, and channel proteins. The autoimmune response is potentiated by cytokines that mediate the activation of Th1, Th2, or Th17 lymphocytes. The released cytokines can also be recognized as autoantigens, meaning they can be targets of the autoimmune response. The effects of autoimmunity on cytokines or their receptors are diverse, and the mechanisms of this type of autoimmune response are discussed in this review.

Background Bronchiectasis is a major respiratory complication in patients with common variable immunodeficiency (CVID) and is associated with recurrent pulmonary infections. However, it is unclear whether other infections or non-infectious respiratory conditions are related to its development. Objective To identify respiratory comorbidities associated with bronchiectasis in patients with CVID. Methods A total of 1470 CVID patients enrolled in the USIDNET registry were included in a cross-sectional analysis. The primary outcome of our study was to determine the clinical characteristics and other respiratory conditions associated with respiratory comorbidities and physician-reported bronchiectasis. Results One hundred ninety-seven CVID patients were noted to have bronchiectasis (13.4%). Affected patients were significantly older than patients without bronchiectasis (median age 54 years vs. 49 years, p = 0.0004). These patients also had lower serum IgA (13 mg/dL IQR 60 mg/dL vs. 28.4 mg/dL IQR 66 mg/dL, p = 0.000). Notably, chronic rhinosinusitis (OR = 1.69 95%CI 1.05–2.75), sinusitis (OR = 2.06 95%CI 1.38–3.09), pneumonia (OR = 2.70 95%CI 1.88–3.88), COPD (OR = 2.66 95%CI 1.51–4.67), and interstitial lung disease (OR = 2.34 95%CI 1.41–3.91) were independently associated with the development of bronchiectasis in this population. Conclusion These data suggest that lower and upper respiratory infections, chronic lower airway disease, and interstitial lung diseases are independently associated with bronchiectasis in CVID patients. Further study into predisposing conditions related to the development of bronchiectasis in CVID patients may allow prediction and early intervention strategies to prevent the development of this complication.

Introducción: la colitis ulcerativa pediátrica (CUP), la enfermedad de Crohn pediátrica (ECP) y la enfermedad inflamatoria intestinal pediátrica no clasificable (EIIPNC) tienen particularidades clínicas y psicosociales que las diferencian de las del adulto y pueden condicionar enfoques terapéuticos distintos por las posibles repercusiones nutricionales, crecimiento y desarrollo, lo que representa un desafío para el pediatra y el gastroenterólogo. Objetivo: desarrollar recomendaciones basadas en la evidencia por consenso de expertos para el diagnóstico y el tratamiento oportunos y seguros de la enfermedad inflamatoria intestinal pediátrica (EIIP) en menores de 18 años, para los profesionales que atienden estos pacientes y los pagadores en salud. Metodología: a través de un panel de expertos del Colegio Colombiano de Gastroenterología, Hepatología y Nutrición Pediátrica (COLGAHNP) y un grupo multidisciplinario se formularon 35 preguntas en relación con el cuadro clínico, el diagnóstico y el tratamiento de la EIIP. A través de una revisión y un análisis crítico de la literatura, con especial énfasis en las principales guías de práctica clínica (GPC), estudios clínicos aleatorizados (ECA) y metaanálisis de los últimos 10 años, los expertos plantearon 77 recomendaciones que respondían a cada una de las preguntas de investigación con sus respectivos puntos prácticos. Posteriormente, cada una de las afirmaciones se sometieron a votación dentro del grupo desarrollador, incluyendo las afirmaciones que alcanzaron > 80 %. Resultados: todas las afirmaciones alcanzaron una votación > 80 %. La EIIP tiene mayor extensión, severidad y evolución hacia la estenosis, enfermedad perianal, manifestaciones extraintestinales y retraso en el crecimiento en comparación con los pacientes adultos, por lo que su manejo debe ser realizado por grupos multidisciplinarios liderados por gastroenterólogos pediatras y prepararlos para una transición a la edad adulta. Los criterios de Porto permiten una clasificación práctica de la EIIP. En la ECP, debemos usar la clasificación de París y debemos realizar ileocolonoscopia y esofagogastroduodenoscopia, ya que el 50 % tienen un compromiso superior, usando el SES-CD (UCEIS/Mayo en CUP) y tomando múltiples biopsias. Los laboratorios iniciales deben incluir marcadores de inflamación, calprotectina fecal y descartar infecciones intestinales. El tratamiento, la inducción y el mantenimiento de la EIIP deben ser individualizados y decididos según la estratificación de riesgo. En el seguimiento se debe usar el Pediatric Crohn Disease Activity Index (PCDAI) y Pediatric Ulcerative Colitis Activity Index (PUCAI) de las últimas 48 horas. Los pacientes con EIIP temprana e infantil, deben ser valorados por inmunólogos y genetistas. Conclusión: se proporciona una guía de consenso con recomendaciones basadas en la evidencia sobre el diagnóstico y los tratamientos oportunos y seguros en los pacientes con EIIP.