Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.

Thymolipoma associated with lymphocytosis in a 6-year-old girl: A case report.

Thymolipoma is a benign and rare tumor that could be found at any age. Thymolipoma associated with the myasthenia gravis, Graves disease, aplastic anemia, and hypogammaglobulinemia was reported previously, but in this case, thymolipoma is associated with lymphocytosis. A 6-year-old girl was brought to the hospital because of a chronic cough. Her evaluation revealed a 130 × 160× 160 mm fat-containing soft tissue mass arising from anterior mediastinum with complete left lung collapse and contralateral mediastinal shift. Her past medical history showed that she had been evaluated and treated unsuccessfully due to severe lymphocytosis two years earlier. Her peripheral blood and bone marrow cell morphology were normal; in contrast, blood cell count and CD flow cytometry showed severe lymphocytosis. The patient's tumor was excised entirely without any complications, and lymphocytosis resolved during the follow-up period. Because the T lymphocytes are developed in the thymus, and more than 80% of cells in CD flow cytometry were T lymphocytes, and the lymphocytosis resolved with tumor removal; therefore, the authors suggested that Thymolipoma could be associated with lymphocytosis.

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

BACKGROUND: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. METHODS: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. RESULTS: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. CONCLUSION: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.

Identification of a novel homozygous frameshift mutation in SLC29A3 gene in a case with H syndrome from Iran.

H syndrome is a rare monogenic autosomal recessive disease with characteristic cutaneous findings and multisystem involvement. The aim of this study is to present an Iranian patient with H syndrome and to describe a novel frameshift mutation in SLC29A3 gene. The patient was diagnosed with a few small areas of hyperpigmentation and accompanying hypertrichosis in the lumbar area of her back. Her clinical phenotypes included short stature, hepatosplenomegaly, facial widespread bilateral telangiectatic lesions, bilateral hypertrophy of the parotid gland, upper extremity flexion contracture, elevated inflammatory markers (ESR, CRP) and diabetes mellitus. The identification of a novel homozygous frameshift mutation (c.307_308delTT, p.F103Ter) in SLC29A3 gene, together with the characteristic clinical manifestations of H syndrome, provided accurate diagnosis for this patient.

Impact of IgE-mediated Food Allergy on Parental Quality of Life in Iranian Patients.

Food allergy is a common disorder especially in the first years of life. Strict avoidance of the responsible food is the most effective therapeutic measure so far. But this continuous vigilance could be stressful for the patient and family and decreases their quality of life (QOL). This survey was designed to evaluate the impact of IgE-mediated food allergy on parental QOL in Iranian patients and to develop a valid Persian version of "Food Allergy Quality Of Life- Parental Burden (FAQL-PB) questionnaire". 90 patients (28 females, 62 males) and their parents who were referred to the clinic of Allergy in Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran were enrolled. The questionnaire was translated with scientific method and its reliability was approved in a pilot study (ICC=0.75, cronbach-α=0.90). Among all patients the most common allergens were wheat (60%) and cow's milk (42%). The patient's age (p=0.02), parent's gender (p=0.004), mother's age (p=0.02), duration of the disease (p=0.048), and allergen multiplicity (p=0.004) were found to have the most significant correlation with family and social activity (FSA) domain. The most meaningful associations were achieved between parent's gender (p<0.001) and emotional issues (EM); as well as meal preparation (MP) with patient's age (p=0.02), parent's gender (p<0.0001) and also allergen multiplicity (p= 0.003); likewise nutrition and health concern (NH) domain with parent's gender (p<0.001). Anaphylaxis's history did not place any burden on each domain. It was concluded that presence of food allergic patients in families could considerably affect all domains of QOL.

Combined immunodeficiency presenting with vaccine-associated paralytic poliomyelitis: a case report and narrative review of literature.

Neurologic abnormalities compatible with vaccine-related poliovirus infection (VAPP) may be a first presentation of some primary immunodeficient patients. The risk of VAPP rises from 1 case per 750 000 in normal population to 1 per 7000 times higher, particularly for persons with agammaglobulinemia and hypogammaglobulinemia. However, there is no appropriate estimation for VAPP occurrence in patients with cellular immunity defects. Herein we report a case of combined immunodeficiency with paralytic complication due to oral polio vaccine and we present a literature review on this topic.

Evaluation of humoral immune function in patients with chronic idiopathic thrombocytopenic purpura.

Coincidence of autoimmune diseases such as immune thrombocytopenic purpura (ITP) with immunodeficiencies has been reported previously in patients who suffered from primary antibody deficiency (PAD). But there is no original study on immunological profiles of ITP patients to find out their probable immune deficiency. In this case-control study, ITP patients' humoral immunity was investigated for diagnosis of PAD in comparison with normal population. To evaluate the humoral immune system against polysaccharide antigens, patients' serum immunoglobulin levels were measured and a 23-valent pneumococcal capsular polysaccharide vaccine (PPV23) was administrated to evaluate the antibody response to vaccination. In this study, 14 out of 36 patients (39%) were diagnosed with antibody mediated immune deficiency including 2 patients (5.5%) with immunoglobulin class deficiency and 4 (11%) with IgG subclass deficiency. The remaining patients suffered from specific antibody deficiency. The most frequent deficiency in ITP patients was specific antibody deficiency.Therefore, immunological survey on ITP patients may be important especially for those who have undergone splenectomy.