Possible Role of Cytomegalovirus in Gastric Cancer Development and Recurrent Macrolide-Resistant Campylobacter jejuni Infection in Common Variable Immunodeficiency: A Case Report and Literature Discussion.

Common variable immunodeficiency (CVID) is the most common symptomatic immunodeficiency in adults. It comprises a group of syndromes whose etiology involves genetic, epigenetic, microbiota, and environmental factors. We present the case of a 46-year-old Caucasian male patient with CVID and an immune dysregulation phenotype. The particular elements of the case consisted of an atypical clinical course, which undoubtedly demonstrates the great variability of clinical manifestations that these types of patients can suffer from, including bacterial and viral infections, autoimmune phenomena, and neoplasia. Notably, the patient suffered from recurrent gastrointestinal infection with macrolide-resistant Campylobacter jejuni and gastroduodenal disease and viraemia by cytomegalovirus (CMV). In addition, CMV was postulated as the main pro-oncogenic factor contributing to the development of early-onset intestinal-type gastric adenocarcinoma, for which the patient underwent gastrectomy. The patient's evolution was difficult, but finally, as a result of the multidisciplinary approach, clinical stabilization and improvement in his quality of life were achieved. Based on our brief literature review, this is the first reported case of this clinical complexity. Our experience could help with the management of future patients with CVID and may also update current epidemiological data on CVID.

Incidence, Management Experience and Characteristics of Patients with Giardiasis and Common Variable Immunodeficiency.

Common variable immunodeficiency (CVID) is an antibody immunodeficiency with a wide variety of clinical and immunological manifestations, and whose genetic cause is found in about 25% of diagnosed cases. Giardia lamblia is one of the main causes of gastrointestinal infections in CVID. 5-Nitroimidazoles are the most used first-line treatment, but nitroimidazole-refractory giardiasis is increasing. Nevertheless, only a few cases of refractory giardiasis in CVID have been reported. This study aimed to determine the incidence of Giardia infection in our CVID cohort, shows our management experience and describes patients' phenotypic features. Clinical data collection, immunological, immunogenetics and microbiology assays were performed, and previous cases of giardiasis in CVID were reviewed. The incidence of symptomatic giardiasis was 12.9%. The main immunological features were undetectable or decreased IgA levels and reduced switched memory B cells. A probable PTEN pathogenic variant was detected in one. Three patients responded to metronidazole but suffered reinfections, and one was a refractory giardiasis eradicated with innovative quinacrine plus paromomycin combination. This work could contribute to the decision-making and therapeutic management of future patients with CVID and giardiasis, highlighting the importance of the early detection and treatment of infections in patients with CVID to ensure a good quality of life.

Common Variable Immunodeficiency Associated with a De Novo IKZF1 Variant and a Low Humoral Immune Response to the SARS-CoV-2 Vaccine.

BACKGROUND AND AIMS: Common variable immunodeficiency (CVID) comprises a group of diseases with heterogeneous clinical and immunological manifestations. Several mutations have been identified in genes encoding proteins essential for immune function. Our aim was to phenotypically and genotypically characterize a patient diagnosed with CVID and study his response to the SARS-CoV-2 vaccine. METHODS: We performed a next-generation sequencing analysis, a CMIA, and an ELISA to analyze the humoral and cellular response to the SARS-CoV-2 vaccine, respectively. We also employed flow cytometry and immunoturbidimetry to assess the patient's global immune status. RESULTS: We found a low humoral but positive cellular response to the SARS-CoV-2 vaccine. NGS screening revealed a transition from guanine to adenine at position c.485 of the IKZF1 gene in heterozygosity, giving rise to the R162Q variant, which was not present in his parents. CONCLUSIONS: The R162Q variant of the IKZF1 gene has been associated with CVID type 13, but always with an autosomal dominant inheritance with high penetrance. Therefore, we present for the first time a case of CVID associated with a de novo heterozygous R162Q variant in the IKZF1 gene in a patient with a low humoral immune response to the complete COVID-19 vaccination program.

References Values of Soluble α-Klotho Serum Levels Using an Enzyme-Linked Immunosorbent Assay in Healthy Adults Aged 18-85 Years.

α-Klotho protein is a powerful predictor of the aging process and lifespan. Although lowered circulating soluble α-Klotho levels have been observed in aged non-healthy individuals, no specific reference values across a wide range of ages and sex using an enzyme-linked immunosorbent assay (ELISA) are available for larger cohorts of healthy individuals. The present analytical cross-sectional study was aimed to establish the reference values of soluble α-Klotho serum levels in healthy adults by age and sex groups. A total of 346 (59% women) healthy individuals aged from 18 to 85 years were recruited. Subjects were divided by sex and age as: (i) young (18−34.9 years), (ii) middle-aged (35−54.9 years), and (iii) senior (55−85 years) individuals. The soluble α-Klotho levels were measured in serum using ELISA. Senior adults were the age-group that presented the lowest soluble α-Klotho serum levels (p < 0.01), with age showing a negative association with soluble α-Klotho serum levels (p < 0.001). No differences between sexes were observed. Therefore, soluble α-Klotho levels were especially decreased­regardless of sex­in our cohort of healthy individuals because of the physiological decline derived from the aging process. We recommend routine assessments of soluble α-Klotho levels using ELISA as a simple and cheap detectable marker of aging that improves quality of life in the elderly.

Body Composition and S-Klotho Plasma Levels in Middle-Aged Adults: A Cross-Sectional Study.

The α-Klotho gene was identified as a possible "aging-suppressor" agent that extends life span when overexpressed. However, little is known about the association of the body composition with the secreted protein form of the α-Klotho gene (S-Klotho). Therefore, the aim of this study was to analyze the association of body composition, including lean and fat mass as well as bone mineral density (BMD), with S-Klotho plasma levels in middle-aged sedentary adults. A total of 74 (39 women) middle-aged sedentary adults (53.7 ± 5.1 years old; 75.7 ± 14.0 kg; 167.8 ± 9.8 cm) participated in the study. We measured weight and height, and we used dual-energy X-ray absorptiometry to measure fat mass and lean mass. We calculated the body mass index (BMI), fat mass index (FMI), and lean mass index (LMI). The S-Klotho plasma levels were measured in the ethylenediaminetetraacetic acid plasma using a solid-phase sandwich enzyme-linked immunosorbent assay. There was a strong positive association between LMI and S-Klotho plasma levels (ß = 74.794, R2 = 0.346, p < 0.001), which persisted after controlling for age and gender as well as after additionally controlling for FMI. Significantly positive associations of BMI and BMD were also found with S-Klotho plasma levels (ß = 33.981, R2 = 0.125, p = 0.002 and ß = 858.194, R2 = 0.058, p = 0.041, respectively), which disappeared after controlling for LMI (ß = 0.183, R2 = 0.611, p = 0.984 and ß = -379.426, R2 = 0.617, p = 0.290, respectively). FMI was not significantly associated with S-Klotho plasma levels. Our study shows that LMI is strongly associated with S-Klotho plasma levels and explains the associations of BMI and BMD with S-Klotho plasma levels in middle-aged sedentary adults.

Exercise training as S-Klotho protein stimulator in sedentary healthy adults: Rationale, design, and methodology.

AIMS: The secreted form of the α-Klotho gene (S-Klotho), which is considered a powerful biomarker of longevity, makes it an attractive target as an anti-ageing therapy against functional decline, sarcopenic obesity, metabolic and cardiovascular diseases, osteoporosis, and neurodegenerative disorders. The S-Klotho plasma levels could be related to physical exercise inasmuch physical exercise is involved in physiological pathways that regulate the S-Klotho plasma levels. FIT-AGEING will determine the effect of different training modalities on the S-Klotho plasma levels (primary outcome) in sedentary healthy adults. FIT-AGEING will also investigate the physiological consequences of activating the klotho gene (secondary outcomes). METHODS: FIT-AGEING will recruit 80 sedentary, healthy adults (50% women) aged 45-65 years old. Eligible participants will be randomly assigned to a non-exercise group, i.e. the control group, (n = 20), a physical activity recommendation from World Health Organization group (n = 20), a high intensity interval training group (n = 20), and a whole-body electromyostimulation group (n = 20). The laboratory measurements will be taken at the baseline and 12 weeks later including the S-Klotho plasma levels, physical fitness (cardiorespiratory fitness, muscular strength), body composition, basal metabolic rate, heart rate variability, maximal fat oxidation, health blood biomarkers, free-living physical activity, sleep habits, reaction time, cognitive variables, and health-related questionnaires. We will also obtain dietary habits data and cardiovascular disease risk factors.

Serum free light chains in the evaluation of the response to treatment and biological progression in primary amyloidosis / Cadenas ligeras libres séricas en la evaluación de la respuesta al tratamiento y progresión biológica en Amiloidosis Primaria

Primary amyloidosis is a rare condition characterised by the deposition of free light chains in different tissues and organs (e.g. kidney, heart, liver, gastrointestinal system). The aim of the therapy in patients with primary amyloidosis is to suppress the monoclonal plasma cells that produce the amyloidogenic free light chains and to preserve the organ function. Thus, the new criteria for the haematological disease response include the measurement of serum free light chains concentrations. The case is presented on a patient diagnosed with primary amyloidosis, where the difference between bound and free serum free light chains (dFLC) was used to evaluate the haematological response to the treatment, as well as any biological progression. In contrast to dFLC, Bence Jones Protein in urine was positive but ineffective to evaluate the response to the treatment (AU)

La amiloidosis primaria es una entidad rara caracterizada por el depósito de cadenas ligeras libres en diferentes tejidos y órganos (riñón, corazón, hígado, aparato gastrointestinal). El objetivo en la terapia de los pacientes con amiloidosis primaria consiste en suprimir las células plasmáticas monoclonales que producen las cadenas ligeras libres amiloidogénicas y preservar la función de los órganos afectados. Así, los nuevos criterios de respuesta hematológica de la enfermedad incorporan la medida de las concentraciones séricas de cadenas ligeras libres. Presentamos el caso de una paciente a quien se diagnosticó amiloidosis primaria y en la cual la diferencia de concentración en suero entre la cadena ligera libre monoclonal implicada y la no implicada (dFLC) nos permitió evaluar la respuesta hematológica al tratamiento y la presencia de progresión biológica. En contraste a la dFLC, la proteinuria de Bence Jones fue positiva pero ineficaz en la evaluación de la respuesta al tratamiento (AU)

Carcinoma de células pequeñas mixto: un desafío diagnóstico / A rare case of combined small-cell lung carcinoma: a challenging diagnosis

Los síndromes neurológicos paraneoplásicos constituyen un conjunto de manifestaciones neurológicas asociadas a la existencia de una tumor oculto no diagnosticado en un paciente. Los síndromes neurológicos paraneoplásicos están producidos por mecanismos inmunológicos donde tiene lugar una respuesta inmunológica frente a antígenos compartidos por el tumor y el tejido neuronal del paciente. La detección serológica de los anticuerpos onconeuronales (Hu, Yo, Ri, Ma-2, anfifisina, etc.) es de utilidad en el diagnóstico de los síndromes neurológicos paraneoplásicos asociados. Presentamos el caso de una paciente que acude a Urgencias por presentar alteraciones neurológicas y donde los resultados obtenidos por el laboratorio clínico permiten orientar el estudio diagnóstico de la paciente hacía la búsqueda de un tumor oculto de estirpe microcítica mixta (AU)

Paraneoplastic neurological syndromes are a set of neurological manifestations associated with the existence of a hidden tumour in a patient. Paraneoplastic neurological syndromes are produced by immunological mechanisms where an immune response occurs against antigens shared between tumour and neuronal tissue of the patient. Serological detection of onconeural antibodies (Hu, Yo, Ri, Ma-2, amphiphysin, etc.) is useful in the diagnosis of associated paraneoplastic neurological syndromes. The case is presented of a patient who was admitted to emergency room due to neurological disorders. With the results of the clinical laboratory, the study was oriented towards the search for a hidden tumour of microcytic mixed lineage (AU)