Seroprevalencia del SARS-CoV-2 en los pacientes con enfermedades inmunomediadas en tratamiento con terapias biológicas y sintéticos dirigidos / Seroprevalence of SARS-CoV-2 antibodies in patients with immune-mediated inflammatory diseases treated with biological and synthetic targeted therapies

INTRODUCCIÓN: La seroprevalencia del SARS-CoV-2 en las enfermedades inflamatorias inmunomediadas (IMID) sigue siendo fuente de controversia. OBJETIVO: Comparar la seroprevalencia de anticuerpos (Ac) anti SARS-CoV-2 en pacientes con IMID en tratamientos con fármacos antirreumáticos modificadores de la enfermedad biológicos (FAMEb) o sintéticos dirigidos (FAMEsd) frente a un grupo de personas sin IMID. MÉTODOS: Estudio de pacientes con IMID y tratamientos con FAMEb y FAMEsd y de individuos sin IMID. Mediante la técnica de inmunoensayo por quimioluminiscencia indirecta, se determinaron las serologías IgG frente al SARS-CoV-2 entre octubre/2020 y mayo/2021. RESULTADOS: Se estudiaron 1.100 sujetos, 550 pacientes con IMID y 550 personas sin IMID. Se observó una seroprevalencia de 16% (88/550) en los pacientes frente a 19,3% (106/550) en el grupo de personas sin IMID, sin significación estadística (OR 0,790 [IC 95% 0,558-1,118]). Comparando los tratamientos con FAMEb o FAMEsd, se observó una tendencia a una menor seroprevalencia con rituximab, en relación con los individuos sin IMID (OR 0,296 [IC 95% 0,0871,007]). Asimismo, se encontró menor seroprevalencia en los pacientes que además de su FAMEb recibían tratamiento con metotrexato, en comparación con el grupo de personas sin IMID (OR 0,432 [IC 95% 0,223-0,835]). CONCLUSIONES: Las IMID en tratamiento con FAMEb o FAMEsd no influyen en la seroprevalencia frente al SARS-CoV-2 de los pacientes. El tratamiento concomitante con metotrexato disminuye de forma significativa la seroprevalencia en estos pacientes.

BACKGROUND: The seroprevalence of SARS-CoV-2 in immunemediated inflammatory diseases (IMID) remains controversial. AIM: To compare the seroprevalence of antibodies (Ab) to SARS-CoV-2 in patients with IMID receiving treatment with biological diseasemodifying antirheumatic drugs (bDMARD) or targeted synthetic (tsDMARD) versus a group of people without IMID. METHODS: Study of patients with IMID and treatments with bDMARD and tsDMARD and individuals without IMID. IgG serology against SARS-CoV-2 was measured using the two-step sandwich immunoassay technique by indirect chemiluminescence between October 2020 and May 2021. RESULTS: A total of 1100 subjects were studied, 550 patients with IMID and 550 persons without IMID. A seroprevalence of 16% (88/550) was observed in patients versus 19.3% (106/550) in the group of people without IMID, without statistical significance (OR 0.790 [95% CI 0.558-1.118]). Comparing the treatments with bD- MARD or tsDMARD, there was a tendency to lower seroprevalence with rituximab, in relation to individuals without IMID (OR 0.296 [95% CI 0.087-1.007]). In addition, lower seroprevalence was found in patients who received methotrexate treatment in addition to their bDMARD, compared to the group of individuals without IMID (OR 0.432 [95% CI 0.223-0.835]). CONCLUSIONS: IMIDs in treatment with bDMARDs or tsDMARDs do not influence the seroprevalence against SARS-CoV-2 in patients. Concomitant treatment with methotrexate significantly decreased seroprevalence in these patients.

A new approach to the study of Hodgkin lymphoma by flow cytometry.

Hodgkin lymphoma (HL) appears to originate from germinal centre B cells but lacks expression of most B cell markers. In contrast to non-Hodgkin B lymphomas, HL is not routinely diagnosed using flow cytometry techniques, and diagnosis is mainly based on immunohistochemical and cytomorphological pathology studies. Hodgkin and Reed-Sternberg cells are large and fragile, making them difficult to study by flow cytometry. The aim of this study was to characterise the CD71 expression pattern on CD4+ T cells from HL patients and to design a simple flow cytometry algorithm to complement the histopathological diagnosis of HL. The present study suggests the utility of a conventional staining protocol with a simple panel of seven markers (CD15, CD30, CD4, CD8, CD71, CD3, and CD45) and a well-defined analysis strategy. The proposed algorithm uses the CD71 ratio (calculated as the percentage of CD71+ CD4+ T cells divided by the percentage of CD71+ CD45+ CD3- lymphocytes), with a cut-off of 0.5 to establish diagnosis groups as suggestive (≥0.5) or not suggestive (<0.5) of HL. In HL, CD71 expression is higher on CD4+ T lymphocytes than on non-T lymphocytes. In addition, the CD4+ T cell population is increased in HL patients, with no change in amounts of CD8+ T cells. Application of the CD71 ratio algorithm yielded a sensitivity of 82% and specificity of 87%, with 84.61% of patients correctly diagnosed. Although histopathology remains the gold standard for definitive HL diagnosis, the proposed flow cytometry method provides a rapid method to guide the study that would allow a more robust and integrated diagnosis. Moreover, the procedure is easily applicable in most clinical laboratories as it does not require state-of-the-art cytometers and uses standard reagents.

CYFRA 21-1 in patients with suspected cancer: evaluation of an optimal cutoff to assess the diagnostic efficacy and prognostic value.

Objectives: Chosen cutoff for cytokeratin 19 fragment antigen (CYFRA 21-1) as a tumor biomarker considerably influences its diagnostic and prognostic usefulness. The aim of the present study is to determine an optimal cutoff value for diagnostic validity of CYFRA 21-1 by Lumipulse ® technology in patients with suspected cancer and also to determine if CYFRA 21-1 levels provide prognostic value. Methods: A consecutive 284 patients suggestive of malignant disease from six hospitals of Madrid were enrolled in a retrospective design. Optimal CYFRA 21-1 cutoff value was obtained by receiver operating characteristic curve and Youden test. The diagnostic validity was evaluated according to sensitivity, specificity, predictive values and likelihood ratios. The prognostic value of CYFRA 21-1 was checked using multiple logistic regression. Thirty-two diagnostic cancers were confirmed. Results: The most optimal cutoff was 3.15 ng/mL. This cutoff showed a better specificity 93.63% (95% confidence interval [CI], 89.66-96.16), positive predictive value 60.98% (95% CI, 44.54-75.38) and positive likelihood ratio 12.65 (95% CI, 7.64-20.95) than the cutoff recommended by Fujirebio® (1.8 ng/mL) (specificity: 73.71% [95% CI, 67.72-78.95], positive predictive value: 29.79% [95% CI, 21.02-40.23] and positive likelihood ratio 3.43 [95% CI, 2.71-4.35]), improving the current diagnostic accuracy. In multivariate analysis, elevated levels of CYFRA 21-1 (>3.15 ng/mL) was confirmed as an unfavorable prognostic factor. Conclusions: The best cutoff for CYFRA 21-1 obtained was 3.15 ng/mL in patients with suspected cancer. This new cutoff decreases the false positive rate and improves the diagnostic efficacy of CYFRA 21-1 as a tumor marker as well as its association with death events.