Noninfectious Complications in B-Lymphopenic Common Variable Immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is considered the most symptomatic type of inborn errors of immunity in humans. Along with infectious complications, which have numerous consequences, noninfectious complications are a major challenge among CVID patients. METHODS: All CVID patients registered in the national database were included in this retrospective cohort study. Patients were divided into 2 groups based on the presence of B-cell lymphopenia. Demographic characteristics, laboratory findings, noninfectious organ involvement, autoimmunity, and lymphoproliferative diseases were evaluated. RESULTS: Among 387 enrolled patients, 66.4% were diagnosed with noninfectious complications and 33.6% with isolated infectious presentations. Enteropathy, autoimmunity, and lymphoproliferative disorders were reported in 35.1%, 24.3%, and 21.4% of patients, respectively. Some complications, including autoimmunity and hepatosplenomegaly, were reported to be significantly more frequent among patients with B-cell lymphopenia. As for organ involvement, the dermatologic, endocrine, and musculoskeletal systems were predominantly affected in CVID patients with B-cell lymphopenia. Among autoimmune manifestations, the frequency of rheumatologic, hematologic, and gastrointestinal autoimmunity was reported to be higher than that of other types of autoimmunity not associated with B cell-lymphopenia. Furthermore, hematological cancers, particularly lymphoma, were the most common type of malignancy. The mortality rate was 24.5%, and respiratory failure and malignancies were the most common causes of death, with no significant differences between the 2 groups. CONCLUSIONS: Considering that some of the noninfectious complications might be associated with B-cell lymphopenia, regular patient monitoring and follow-up with proper medication (in addition to immunoglobulin replacement therapy) are highly recommended to prevent sequelae and increase patient quality of life.

Non-Infectious Complications in B-Lymphopenic Common Variable Immunodeficiency.

BACKGROUND AND OBJECTIVE: Common variable immunodeficiency (CVID) is considered the most symptomatic type of inborn errors of immunity in humans. Along with infectious complications, which have numerous consequences, non-infectious complications are also a major challenge among CVID patients. METHODS: All registered CVID patients in the national database were included in this retrospective cohort study. Patients were divided into two groups based on the presence of B-cell lymphopenia. Demographic characteristics, laboratory findings, non-infectious organ involvements, autoimmunity, and lymphoproliferative diseases were evaluated. RESULTS: Among 387 enrolled patients, 66.4% were diagnosed with non-infectious complications; however, 33.6% had only infectious presentations. Enteropathy, autoimmunity, and lymphoproliferative disorders were reported in 35.1%, 24.3%, and 21.4% of patients, respectively. Some complications, including autoimmunity and hepatosplenomegaly, were reported to be significantly higher among patients with B-cell lymphopenia. Among organ involvement, dermatologic, endocrine and musculoskeletal systems were predominantly affected in CVID patients with B-cell lymphopenia. Among autoimmune manifestations, the frequency of rheumatologic, hematologic, and gastrointestinal autoimmunity was reported to be higher compared to other types of autoimmunity independent from the B cell-lymphopenia. Furthermore, hematological cancers, particularly lymphoma, were slightly introduced as the most common type of malignancy. Meanwhile, the mortality rate was 24.5%, and respiratory failure and malignancies were reported as the most common cause of death in our patients without significant differences between the two groups. CONCLUSION: Considering that some of the non-infectious complications might be associated with B-cell lymphopenia, therefore, regular patient monitoring and follow-up along with proper medications (besides immunoglobulins replacement therapy) are highly recommended to prevent further sequels and increase the patients' quality of life.

Sustained unresponsiveness development in wheat oral immunotherapy: predictive factors and flexible regimen in the maintenance phase.

Summary: Background. Immunotherapy may induce sustained unresponsiveness (SU )in which the patient can tolerate the allergen without any severe symptoms after discontinuing immunotherapy. The present study evaluated serum and cutaneous markers for predicting SU in patients with wheat anaphylaxiswho underwent oral immunotherapy. We investigated the effectiveness of a flexible regimen of 5 to 10 g wheat protein (WP) in the maintenance phase of oral immunotherapy (OIT). Methods.This study was conducted on 19 patients with wheat anaphylaxis who underwent OIT. The results of the skin prick test (SPT), besides specific serum IgE (sIgE) and IgG4 (sIgG4) to WP, were evaluated before the desensitization. The maintenance dose started from the preferred dose of 5 to 10 g WP after the build-up phase, if the patient could tolerate it. All patients were recruited 7 to 9 months after undergoing this flexible regimen, and the results of SPT and sIgE, and sIgG4l evels were obtained once more. The patients underwent oral food challenge (OFC) after a 3-4-week avoidance to evaluate SU. Results. There was anassociation between mean IgE reduction and SU (p < 0.0006), while no association was observed between the mean increase in specific IgG4 (p = 0.1), and the mean wheal diameter decrease (p = 0.29). A 50% reductionin sIgE was associated with SU. Thirteen patients were considered to havea SU. There was no association between the flexible regimen and the desensitization rate. Conclusions.The reduction of 50% sIgE is a predictive factor for SU in patients with IgE-mediated wheat allergy.

Can concurrent lower gastrointestinal manifestations help the timely diagnosis of small intestinal bacterial overgrowth in CVID patients?.

Summary: Introduction and objective. Gastrointestinal complications are considered as one of the most common manifestations in patients with Common Variable Immunodeficiency (CVID). These complications can result from Small Intestinal Bacterial Overgrowth (SIBO). Hydrogen breath test is extensively used to diagnose SIBO. The objective of this study was to evaluate the prevalence of SIBO using the Hydrogen Breath Test (HBT) in patients with CVID. Materials and methods. Twenty-seven patients with CVID entered this cross-sectional study. Demographic and lower gastrointestinal symptoms were recorded in a check list. Hemoglobin level was measured in all patients. The concentration of IgA and IgG was assessed using nephelometry. Moreover, SIBO was detected by means of Glucose hydrogen breath test. Results. The mean (plus-minus SD) age of the patients was 35.25 (plus-minus 11.69) years. Twenty patients (74.1%) manifested at least one lower gastrointestinal symptom. The most frequent lower gastrointestinal manifestations were bloating (66.7%) and chronic diarrhea (40.7%), respectively. IgA level less than 10 mg/dl and IgG level less than 600 mg/dl were determined in 77.8% and 25.9% of patients, respectively. Positive HBT was detected in 40.7% (n = 11) of the patients. In the positive HBT group, bloating, chronic diarrhea and abdominal pain were the most common lower GI manifestations. There was no significant difference in terms of age, BMI, IgA level, and duration of CVID between the positive and negative HBT groups. The significant association of co-occurrence of anemia and abdominal pain with positive HBT (positive predictive value: 100%) might be considered as a clue to SIBO diagnosis. Conclusions. Regarding the high prevalence and non-specific manifestation of SIBO, it is suggested to consider concurrent symptoms in patients with CVID to manage the timely and precise diagnosis of SIBO.

Assessment of IgE- and cell-mediated immunity in pediatric patients with eosinophilic esophagitis.

Summary: Eosinophilic esophagitis (EoE) is a chronic allergen/immune-mediated disease leading to esophageal dysfunction. Food allergens play critical roles in the pathogenesis and treatment of EoE via different mechanisms. This study aimed to present the characteristics and evaluate the ability of skin prick test (SPT), skin prick to prick test (SPP) (IgE-mediated), and atopic patch test (APT) (cell-mediated) individually or simultaneously to diagnose food allergy in patients suffering from EoE. This prospective study was conducted on 58 patients with EoE. Seven patients (12.1%) were positive to only one, 3 (5.2%) were simultaneously positive to two, and 32 (55.2%) were simultaneously positive to three tests. Single and double sensitizations were totally 10.4% in IgE-mediated reactions, while 36.5% in cell-mediated reactions. In contrast, poly sensitization (> 2 allergens) was 51.7% in IgE-mediated tests and 20.7% in the cell-mediated test. Multiple sensitization findings showed egg white, milk, yolk, and soy were the most frequent allergens. Our findings indicate that EoE is early onset and associated with multiple food sensitizations, particularly via IgE-mediated mechanisms. These immune-mediated responses encompass both IgE-mediated (SPT and SPP) and cell-mediated (APT) reactions simultaneously not individually. Therefore, employing multiple assays may strengthen the diagnosis of food sensitization.

Clinical, Laboratory, and Molecular Findings for 63 Patients With Severe Combined Immunodeficiency: A Decade´s Experience.

BACKGROUND: Severe combined immunodeficiency (SCID) is a life-threatening pediatric disease. We report on the clinical evaluation, immunological assessment, molecular analysis, and outcomes of SCID patients in a tertiary referral center in Iran. METHODS: From January 2006 to December 2015, we performed a prospective cohort study in which initial screening and advanced immunological tests were carried out on patients suspected of having SCID. Genetic analysis was also performed to confirm the diagnosis. RESULTS: A total of 63 patients were diagnosed with SCID (43 male [68.3%]). The median age at onset and diagnosis and diagnostic delay were 40 and 110 and 60 days respectively. A total of 49 patients (77.8%) had a history of BCG vaccination, and of these, one-third experienced BCG-associated complications. The most common clinical manifestations were pneumonia, recurrent oral candidiasis, chronic diarrhea, and failure to thrive. Of the thirteen patients who underwent hematopoietic stem cell transplantation, 8 survived and 5 died before they could receive the transplant. Most patients (34.9%) were classified as having T-B-NK+ SCID and had a mutation in the RAG2 or RAG1 gene. CONCLUSIONS: Autosomal recessive SCID is the most common type in Iranian patients. Providing high-quality training to physicians and patients' families to reduce the diagnostic delay should be prioritized. It is also important to raise awareness of live vaccination and to expand stem cell donor registries to speed up the transplantation process.

Clinical, laboratory, and molecular findings for 63 patients with severe combined immunodeficiency: a decade's experience

Introduction: Severe combined immunodeficiency (SCID) is a life-threatening pediatric disease. We report on the clinical evaluation, immunological assessment, molecular analysis, and outcomes of SCID patients in a tertiary referral center in Iran. Methods: From January 2006 to December 2015, we performed a prospective cohort study in which initial screening and advanced immunological tests were carried out on patients suspected of having SCID. Genetic analysis was also performed to confirm the diagnosis. Results: A total of 63 patients were diagnosed with SCID (43 male [68.3%]). The median age at onset and diagnosis and diagnostic delay were 40 and 110 and 60 days respectively. A total of 49 patients (77.8%) had a history of BCG vaccination, and of these, onethird experienced BCG-associated complications. The most common clinical manifestations were pneumonia, recurrent oral candidiasis, chronic diarrhea, and failure to thrive. Of the thirteen patients who underwent hematopoietic stem cell transplantation, 8 survived and 5 died before they could receive the transplant. Most patients (34.9%) were classified as having T-B-NK+ SCID and had a mutation in the RAG2 or RAG1 gene. Conclusion: Autosomal recessive SCID is the most common type in Iranian patients. Providing high-quality training to physicians and patients’ families to reduce the diagnostic delay should be prioritized. It is also important to raise awareness of live vaccination and to expand stem cell donor registries to speed up the transplantation process (AU)

Introducción: La inmunodeficiencia combinada severa (SCID) es una grave enfermedad pediátrica que puede comprometer la vida del paciente. El artículo recoge la evaluación clínica e inmunológica, el análisis molecular y la supervivencia de los pacientes con SCID atendidos en un hospital de referencia de Irán. Métodos: Desde enero de 2006 a diciembre de 2015, se realizó un estudio prospectivo en los pacientes con SCID en el que se realizó un screening inicial junto a diferentes análisis inmunológicos. Se realizó un análisis genético para confirmar el diagnóstico. Resultados: Sesenta y tres pacientes fueron diagnosticados de SCID, cuarenta y tres (63,8%) de los mismos eran varones. La mediana de la edad de inicio de la enfermedad, diagnóstico y retraso en su diagnóstico, fueron de 40, 110 y 60 días respectivamente. Cuarenta y nueve pacientes (77,8%) recibieron vacunación con BCG y un tercio de los mismos presentó complicaciones como consecuencia de la misma. Las manifestaciones clínicas más frecuentes de estos pacientes fueron: neumonía, candidiasis oral recidivante, diarrea crónica y retraso en el crecimiento. Ocho de los treces pacientes que recibieron trasplante de progenitores hematopoyéticos, lograron sobrevivir. Los restantes pacientes fallecieron antes de poder recibir dicho trasplante. El 34,9% de los pacientes tuvieron T-B-NK+ SCID y la mayoría de los pacientes eran portadores de mutaciones en los genes RAG2 o RAG1. Conclusión: La variante autosómica recesiva de la SCID es la forma más común en los pacientes iraníes. Se debe considerar prioritario proporcionar una formación adecuada a los médicos y las familias para reducir el retraso en el diagnóstico. Es igualmente importante concienciar para evitar la vacunación con gérmenes vivos y expandir los registros de donantes de células madre para agilizar el trasplante de estos pacientes (AU)

Long-term follow-up of ninety eight Iranian patients with primary immune deficiency in a single tertiary centre

PURPOSE: The aim was to describe the clinical manifestations, complications and long-term outcome of a cohort of Iranian patients with primary immune deficiency (PID). METHOD: We retrospectively studied the demographic, clinical and immunological characteristics of the PID patients in a single tertiary centre, from January 1989 to July 2014. The patients were classified according to the International Union of Immunological Societies Expert Committee on PID. RESULTS: 98 patients were diagnosed with and followed-up for 15 disorders. The mean age at onset and diagnosis and the diagnostic delay were 8±10, 14.2±13.1 and 6.1±7 years, respectively. Parental consanguinity rate was 57%. Predominantly Antibody Deficiency was the most common diagnosis (n=63), followed by congenital defects of phagocytes (n=16), combined immunodeficiencies (n=12), well defined syndromes (n=4) and defects in innate immunity (n=3). Recurrent sinopulmonary infection was the most common presentation. Active infections were treated appropriately, in addition to prophylactic therapy with IVIG and antimicrobials. Not all the patients were compliant with prophylactic regimens due to cost and unavailability. One SCID patient underwent successful bone marrow transplantation. The total mortality rate was 19% during the follow-up period (7.8±7.6 years). The mean age of living patients at the time of study was 23±11.7 years. CONCLUSIONS: Physicians awareness of PID has been rising dramatically in Iran, ensuring an increasing number of patients being diagnosed and treated. More effective treatment services, including health insurance coverage and drug availability are needed to improve the outcome of PID patients

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Work ability index among healthcare personnel in a university hospital in Tehran, Iran.

BACKGOUND: Work ability is an important issue from a social point of view, as it is essential for workers health and welfare. OBJECTIVE: This study aimed to determine work ability among healthcare personnel and to investigate its relationship with demographic and lifestyle-related factors. METHODS: Data were collected using the Work Ability Index (WAI) questionnaire among 517 personnel of a hospital in Tehran, Iran. RSULTS: Findings showed a mean WAI of 40.3 (±5.2) for the study population. Work ability was significantly lower in the older personnel and higher for men. A significant correlation was observed between BMI and exercise activity and WAI score. Moreover, employees with experience of less than five years had significant higher work ability than those with 16-20 years of service. CONCLUSIONS: Considering the young study population, it seems the mean WAI is not as desirable. The use of lifestyle promoting programs, besides workplace interventions, can be an effective strategy to increase work ability among healthcare workers.

Long-term follow-up of ninety eight Iranian patients with primary immune deficiency in a single tertiary centre.

PURPOSE: The aim was to describe the clinical manifestations, complications and long-term outcome of a cohort of Iranian patients with primary immune deficiency (PID). METHOD: We retrospectively studied the demographic, clinical and immunological characteristics of the PID patients in a single tertiary centre, from January 1989 to July 2014. The patients were classified according to the International Union of Immunological Societies Expert Committee on PID. RESULTS: 98 patients were diagnosed with and followed-up for 15 disorders. The mean age at onset and diagnosis and the diagnostic delay were 8±10, 14.2±13.1 and 6.1±7 years, respectively. Parental consanguinity rate was 57%. Predominantly Antibody Deficiency was the most common diagnosis (n=63), followed by congenital defects of phagocytes (n=16), combined immunodeficiencies (n=12), well defined syndromes (n=4) and defects in innate immunity (n=3). Recurrent sinopulmonary infection was the most common presentation. Active infections were treated appropriately, in addition to prophylactic therapy with IVIG and antimicrobials. Not all the patients were compliant with prophylactic regimens due to cost and unavailability. One SCID patient underwent successful bone marrow transplantation. The total mortality rate was 19% during the follow-up period (7.8±7.6 years). The mean age of living patients at the time of study was 23±11.7 years. CONCLUSIONS: Physicians awareness of PID has been rising dramatically in Iran, ensuring an increasing number of patients being diagnosed and treated. More effective treatment services, including health insurance coverage and drug availability are needed to improve the outcome of PID patients.

First report of asthma prevalence in Afghanistan using international standardized methods.

No data on the prevalence of asthma in Afghanistan have been published before. In a school-based survey in 2010-2011 the wheezing section of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was completed by a random sample of 1500 children aged 6-7 years and 1500 adolescents aged 13-14 years old. The prevalence of physician-diagnosed asthma was 12.5% in 6-7-year-olds and 17.3% in 13-14-year-olds (P = 0.002). The prevalence of wheeze in the last 12 months was similar in children and adolescents (19.2% and 21.7% respectively). The prevalence of ever wheezing, night attacks, speech-limiting wheeze and exercise-induced wheeze was 23.1%, 4.8%, 12.2% and 9.6% respectively in children and 30.5%, 4.4%, 13.0% and 13.6% respectively in adolescents. These rates are higher than those in neighbouring countries. This first epidemiological survey of asthma in Afghanistan shows that asthma and wheezing are common in Kabul students.

RAD50 single-nucleotide polymorphism in predominantly antibody deficiency

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First report of asthma prevalence in Afghanistan using international standardized methods

No data on the prevalence of asthma in Afghanistan have been published before. In a school-based survey in 2010–2011 the wheezing section of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was completed by a random sample of 1500 children aged 6–7 years and 1500 adolescents aged 13–14 years old. The prevalence of physician-diagnosed asthma was 12.5% in 6–7-year-olds and 17.3%in 13–14-year-olds (P = 0.002). The prevalence of wheeze in the last 12 months was similar in children and adolescents (19.2% and 21.7% respectively). The prevalence of ever wheezing, night attacks, speech-limiting wheeze and exercise-induced wheeze was 23.1%, 4.8%, 12.2% and 9.6% respectively in children and 30.5%, 4.4%, 13.0% and 13.6% respectively in adolescents. These rates are higher than those in neighbouring countries. This first epidemiological survey of asthma in Afghanistan shows that asthma and wheezing are common in Kabul students.

Aucune donnée sur la prévalence de l’asthme en Afghanistan n’a encore été publiée. Dans une enquête en milieu scolaire de 2010 à 2011, la partie sur les sibilances du questionnaire International Study of Asthma and Allergies in Childhood (ISAAC) a été remplie par un échantillon aléatoire de 1500 enfants âgés de 6 à 7 ans etde 1500 adolescents âgés de 13 à 14 ans. La prévalence du diagnostic d’asthme posé par un médecin était de 12,5 % chez les enfants de 6 à 7 ans et de 17,3 % chez les adolescents de 13 à 14 ans (P = 0,002). La prévalence des sibilances au cours de 12 mois précédents était similaire chez les enfants et chez les adolescents (19,2 % et 21,7 %, respectivement). La prévalence des sibilances, des crises nocturnes, des sibilances limitant la parole et d’une respiration sifflante induite par l’exercice était de 23,1 %, 4,8 %, 12,2 % et 9,6 %, respectivement chez les enfants et de 30,5 %, 4,4 %, 13,0 % et 13,6 % respectivement chez les adolescents. Ces pourcentages sont supérieurs à ceuxdes pays voisins. La première enquête épidémiologique sur l’asthme en Afghanistan révèle que l’asthme et les sibilances sont fréquents chez les élèves de Kaboul.

AICDA single nucleotide polymorphism in common variable immunodeficiency and selective IgA deficiency

BACKGROUND: Primary antibody deficiencies (PADs) are a heterogeneous group of disorders, characterised by increased susceptibility to recurrent bacterial infections. Common variable immunodeficiency (CVID) is the most important PAD from the clinical point of view and selective IgA deficiency (IgAD) is the most common PAD. However, the underlying gene defect in both is still unknown. As a recent study in Europe showed an association between a single nucleotide polymorphism (SNP) of AICDA gene with PADs, this study was performed to evaluate such an association in Iranian patients. METHODS: Fifty-eight patients with PAD, including 39 CVID and 19 IgAD, as well as 34 healthy volunteers, were enrolled in this study. Genotyping was done in all groups for an intronic SNP in AICDA (rs2580874), using real-time PCR genotyping assay. RESULTS: The less frequent genotype of AICDA in IgAD patients was AA, seen in 10.5% of the patients, which was much lower than the 30.8% in CVID patients and 38.2% in the controls. However, these differences were not significant. Indeed the GG genotype in the patients with PADs was seen in 20.7%, compared to 8.8% in the controls without any significant difference. CONCLUSIONS: There was no significant association between the previously reported genetic variant of AICDA gene and the development of CVID or IgAD, but further multi-center studies are also needed

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Increased level of interleukin-13, but not interleukin-4 and interferon-γ in chronic rhinosinusitis with nasal polyps

BACKGROUND: This study was performed to investigate the serum level of interleukin (IL)-13, IL-4, and interferon (IFN)-γ in chronic rhinosinusitis with nasal polyps (CRSwNP) and subsequent inflammation pattern and comorbidities including asthma and aspirin intolerance. METHODS: A case-control study was conducted on 60 adult patients with CRSwNP with mean age of 37.7 ± 12.7 (ranging from 18 to 70) years, and on 20 healthy controls. Serum levels of IL-13, IL-4, and IFN-γ were assessed, using enzyme-linked immunosorbent assay to be compared between case and control groups. Serum level of total immunoglobulin (Ig) E was also assessed in the patients with CRSwNP. RESULTS: Serum level of IL-13 in the patients with CRSwNP was significantly higher than the controls (0.98 ± 1.56 vs. 0.34 ± 0.16 pg/ml, respectively, p = 0.002). IL-4 and IFN-γ did not differ significantly between the two groups. Total IgE level was significantly increased in the patients with CRSwNP, compared to the normal values (301.43 ± 516.54 IU/ml, p = 0.033). Among the patients with CRSwNP, 12/60 (20%) had aspirin intolerance and 44/60 (73.3%) had asthma. IgE was also higher in asthmatics than non-asthmatics patients (364.9 ± 586.6 vs. 126.7 ± 135.7, respectively, p = 0.015). Patients with aspirin intolerance had higher levels of IFN-γ (4.7 ± 1.4 vs. 4.1 ± 0.6, respectively, p = 0.022). CONCLUSIONS: IL-13 with high level of total IgE was observed in the patients with CRSwNP, which predisposes them to have concomitant asthma. IFN-γ seems to be down-regulated in the patients with CRSwNP, but could be over-expressed in the presence of aspirin intolerance

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Could oral administration of immunoglobulin reduce diarrheal severity in common variable immunodeficiency?

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Non-Hodgkin's lymphoma in a patient with leucocyte adhesion deficiency

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