Association of NK cell subsets and cytotoxicity with FCGR3A gene polymorphism in functional NK cell deficiency.

OBJECTIVE: The purpose of this study was to assess the association between clinical, laboratory, and functional analyses and polymorphism in the FCGR3A gene in individuals with functional NK cell deficiency. METHODS: A total of 15 functional NK cell deficiency patients and 10 age-matched healthy controls underwent NK cell subgroup, cytotoxicity, and FCGR3A whole-exome analysis with next-generation sequencing. RESULTS: Three different NK cell subsets (CD56brightCD16neg, CD56brightCD16int, and CD56dimCD16hi) were identified. No statistically significant difference was found in the ratio of CD56brightCD16neg cells between patients and controls. CD56brightCD16int and CD56dimCD16hi ratios were found to be significantly lower in patients. As a result of NK cell cytotoxicity analysis, a proportional decrease of K562 amount between patients and controls was found to be statistically significant (p<0.001). In the FCGR3A whole-exome analysis, all patients were found to be homozygous mutant for the c.526G > T (p.V176F) in exon 4, while three patients were homozygous wild type and 12 patients were heterozygous for the c.197T>A (p.L66H) in exon 3. CONCLUSION: In this study, a group of pediatric patients with suspected functional NK cell deficiency were evaluated and the findings indicated that NK subsets, cytotoxicity results, and FCGR3A gene polymorphism were found to be correlated with the clinical features. We conclude that this kind of study might contribute to follow-up the patients in time.

Evaluation of transcription factors and cytokine expressions of T-cell subsets in CD19 deficiency and their possible relationship with autoimmune disease.

CD19 deficiency is a rare, predominantly antibody deficiency, and there are few studies showing that it can be seen in autoimmune diseases. The aim of study was evaluated to transcription factor and cytokine expressions of helper T (Th)-cell subsets in CD19 deficiency and the possible mechanism role of this factor expression in autoimmune disease. Transcription factor and cytokine expressions of Th1, Th2, Th17, and regulatory T (Treg) cells were investigated by real-time polymerase chain reaction (qPCR) method. In the study, in the patient/control comparison, transcription factor and cytokine expressions of Th1 (T-bet, STAT1, and STAT4) were found to be significantly downregulated, but IFN-γ was significantly upregulated in patients. Th2 factor GATA3, STAT6, IL-4, and IL-5 were significantly downregulated. For Th17, RORγt was downregulated while IL-22 was upregulated. In the heterozygous/control comparison, there was no significant change in gene expressions other than IL-5. T-bet, STAT1, GATA3, IL-4, RORγt, FoxP3, and TGF-ß were significantly downregulated in the patient/heterozygous comparison. It was revealed for the first time that the expression of the transcription factors and cytokines in CD19 deficiency. These findings might be showing the predominance of Th1 factors and suppressed Treg factors which could be related with autoimmunity in CD19 deficiency.

Intraoral and maxillofacial abnormalities in patients with autosomal dominant hyper-IgE syndrome.

Autosomal dominant hyper-IgE syndrome (AD-HIES) is an inborn error of immunity (IEI) caused by a dominant-negative mutation in the signal transducer and activator of transcription 3 (STAT 3). This disease is characterized by chronic eczematoid dermatitis, recurrent staphylococcal skin abscesses, pneumonia, pneumatoceles, and extremely high serum IgE levels. Loss-of-function STAT3 mutations may also result in distinct non-immunologic features such as dental, facial, skeletal, and vascular abnormalities, central nervous system malformations and an increased risk for bone fractures. Prophylactic treatment of Candida infections and prophylactic antimicrobial therapy for staphylococcal skin infections and sinopulmonary infections are essential. An awareness of the oral and maxillofacial features of HIES may facilitate early diagnosis with genetic counselling and may improve future patient care. This study describes oral, dental, and maxillofacial manifestations in 14 patients with genetically defined AD-HIES. We also review the literature and propose recommendations for the complex care of patients with this rare primary immunodeficiency.

Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency.

BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency (LRBA-/-) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA4+/-) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown. OBJECTIVE: Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up. METHODS: The 98 patients (63 LRBA-/- and 35 CTLA4+/-) were followed and evaluated at baseline and every 6 months for clinical manifestations and response to the respective therapies. RESULTS: The LRBA-/- patients exhibited a more severe disease course than did the CTLA4+/- patients, requiring more immunosuppressants, abatacept, and HSCT to control their symptoms. Among the 58 patients who received abatacept as either a primary or rescue therapy, sustained complete control was achieved in 46 (79.3%) without severe side effects. In contrast, most patients who received immunosuppressants as primary therapy (n = 61) showed either partial or no disease control (72.1%), necessitating additional immunosuppressants, abatacept, or transplantation. Patients with partial or no response to abatacept (n = 12) had longer disease activity before abatacept therapy, with higher organ involvement and poorer disease outcomes than those with a complete response. HSCT was performed in 14 LRBA-/- patients; 9 patients (64.2%) showed complete remission, and 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT and abatacept therapy gave rise to similar probabilities of survival. CONCLUSIONS: Abatacept is superior to immunosuppressants in controlling disease manifestations over the long term, especially when started early, and it may provide a safe and effective therapeutic alternative to transplantation.

Defective Treg generation and increased type 3 immune response in leukocyte adhesion deficiency 1.

In 15 Turkish LAD-1 patients and controls, we assessed the impact of pathogenic ITGB2 mutations on Th17/Treg differentiation and functions, and innate lymphoid cell (ILC) subsets. The percentage of peripheral blood Treg cells, in vitro-generated induced Tregs differentiated from naive CD4+ T cells were decreased despite the elevated absolute counts of CD4+ cells in LAD-1 patients. Serum IL-23 levels were elevated in LAD-1 patients. Post-curdlan stimulation, LAD-1 patient-derived PBMCs produced more IL-17A. Additionally, the percentages of CD18-deficient Th17 cells expanded from total or naïve CD4+ T cells were higher. The blood ILC3 subset was significantly elevated in LAD-1. Finally, LAD-1 PBMCs showed defects in trans-well migration and proliferation and were more resistant to apoptosis. Defects in de novo generation of Tregs from CD18-deficient naïve T cells and elevated Th17s, and ILC3s in LAD-1 patients' peripheral blood suggest a type 3-skewed immunity and may contribute to LAD-1-associated autoimmune symptoms.

Atypical Localization of Eczema Discriminates DOCK8 or STAT3 Deficiencies from Atopic Dermatitis.

PURPOSE: Autosomal recessive dedicator of cytokinesis 8 (DOCK8-/-) and autosomal dominant signal transducer and activator of transcription 3 (STAT3-/+) deficiencies are inborn errors of immunity (IEI) disorders present with the classic features of eczema and create a dilemma during differentiation from atopic dermatitis (AD). Therefore, an appropriate approach is required for eczema to diagnose DOCK8-/- and STAT3-/+ early. Here, we described a set of clinical and immunological variables, including atypical AD localizations and lymphocyte subsets, to differentiate DOCK8-/- or STAT3-/+ from AD. METHODS: This multicenter study involved 100 patients with DOCK8-/- and STAT3-/+ and moderate/severe AD. We recruited disease manifestations, including detailed localizations of eczema, infections, and allergy. Principle component analysis (PCA) was used to discriminate DOCK8-/- or STAT3-/+ from AD. RESULTS: There were 43 patients with DOCK8-/-, 23 with STAT3-/+, and 34 with AD. Pneumonia, severe infections, mucocutaneous candidiasis, and skin abscesses were commonly observed in DOCK8 and STAT3 deficiencies. Atypical skin involvement with neonatal rash, retro auricular, axillary, sacral, and genital eczema discriminate DOCK8-/- and STAT3-/+ from AD with high specificity ranges between 73.5 and 94.1% and positive predictive index ranges between 55 and 93.1%. Together with using absolute numbers of CD3+, CD4+, and CD8+ T cells, the combined clinical and laboratory features showed perfect differentiation between DOCK8-/- or STAT3-/+ and AD via PCA. CONCLUSIONS: The described features can be easily implemented by physicians providing early diagnosis of DOCK8 and STAT3 deficiencies.

Successful treatment of postinfectious bronchiolitis obliterans with gamma globulin in a tertiary center: 10 years of experience.

INTRODUCTION: Bronchiolitis obliterans is characterized by partial or total occlusion of the bronchioles due to inflammation and fibrosis, and the most common form is postinfectious bronchiolitis obliterans (PIBO). This study aimed to retrospectively present our intravenous immunoglobulin (IVIG) treatment experience in PIBO patients with a clinically severe course despite receiving commonly used treatment protocols. MATERIALS AND METHODS: The study included patients aged 0-18 with subtle immunological abnormalities who were followed up in our center for PIBO between 2010 and 2021. Clinical evaluation, body mass index (BMI), computerized tomography (CT) image scoring, and immunological parameters were recorded before and after IVIG treatment. RESULTS: Of the 11 patients included in the study, 90% were male, the mean age at diagnosis was 27.1 months (range: 5-68 months) and the mean current age was 81.4 months (range: 15-188 months). The number of hospital visits due to infection and the frequency of hospitalizations decreased markedly in the patients who underwent IVIG therapy. Oxygen therapy was discontinued in all patients, and improvements in radiological severity scores were observed. BMI z-scores improved over the baseline values after IVIG therapy. CONCLUSION: Corticosteroids are considered the best first-line treatment to control inflammation in PIBO. In our study group, PIBO patients showed favorable clinical and radiological responses to regular IVIG treatment, possibly due to minor immune deficiency secondary to steroids or as a result of undetected adaptive and innate immune defects involved in the etiology of severe PIBO.

Retrospective analysis of patients with severe combined immunodeficiency and alternative diagnostic criteria: A 20-year single centre experience.

Severe combined immunodeficiency (SCID) is an inborn errors of immunity (IEI) disorder characterized by impairment in the development and function of lymphocytes and could be fatal if not treated with hematopoietic stem cell transplant in the first 2 years of life. There are various diagnostic criteria for SCID among different primary immunodeficiency societies. We retrospectively evaluated clinical and laboratory findings of 59 patients followed up with the diagnosis of SCID at our clinic over the past 20 years in order to develop an algorithm that would help diagnosis of SCID for the countries where a high ratio of consanguineous marriage is present because these countries have not launched TREC assay in their newborn screening programs. The mean age at diagnosis was 5.80 ± 4.90 months, and the delay was 3.29 ± 3.99 months. The most common complaint and physical examination findings were cough (29.05%), eczematous rash (63%) and organomegaly (61%). ADA (17%), Artemis (14%), RAG1/2 (15%), MHC Class II (12%) and IL-2R (12%) deficiencies were the most common genetic defects. Lymphopenia (87.5%) was the most frequent abnormal laboratory finding and below 3000/mm3 in 95% of the patients. The CD3+ T cell count was 300/mm3 and below in 83% of the patients. As a result, a combination of low lymphocyte count and CD3 lymphopenia for SCID diagnosis would be more reliable for countries with high rate of consanguineous marriage. Physicians should consider diagnosis of SCID in a patient presenting with severe infections and lymphocyte counts below 3000/mm3 under 2 years of age.

Clinical and laboratory evaluation of Turkish children with IgG subclass deficiency.

BACKGROUND: IgG subclass deficiency is a laboratory diagnosis and becomes important with recurrent infections. This study aimed to examine the demographic, clinical, and laboratory results of pediatric cases with IgG subclass deficiency and to improve the understanding of the clinical significance of IgG subclass deficiency. METHODS: In this study, the clinical and laboratory features of 111 pediatric patients, with at least one whose serum IgG subclasses was measured as lower than 2 standard deviation of healthy aged-matched control values, were evaluated. The clinical and laboratory features of the cases with isolated IgG subclass deficiency (Group 1) and those with low serum levels of any of IgG, IgA, and IgM in addition to the IgG subclass deficiency (Group 2) were compared. RESULTS: A total of 55 (49.54%) and 56 (50.45%) patients were included in Groups 1 and 2, respectively. Among our studied cases, 20 (18.1%) had a history of hospitalization in the neonatal period, 61 (54.95%) had at least one hospitalization due to infection, and 55 (49.54%) had a history of recurrent infection. The frequencies of these three conditions were statistically significantly higher in Group 2 (p < 0.05). The frequencies of infections in the last year in Groups 1 and 2 were 4.4 ± 1.2 and 5.4 ± 1.9, respectively (p < 0.05). As a result of recurrent infections, 43.24% (n = 48) of our patients received antibiotic prophylaxis, and 21.62% (n = 24) had immunoglobulin replacement therapy. Furthermore, the numbers of patients who needed these treatments were higher in Group 2 (p < 0.05). CONCLUSION: In cases with IgG subclass deficiencies, concomitant main-group immunoglobulin deficiencies may increase the number and severity of infections, leading to hospitalizations, antibiotic prophylaxis, and immunoglobulin therapy. More attention should be paid to cases of immunoglobulin main-group deficiencies in the follow-up of these cases.

The Middle East and North Africa Diagnosis and Management Guidelines for Inborn Errors of Immunity.

Human inborn errors of immunity (IEI) are a group of 485 distinct genetic disorders affecting children and adults. Signs and symptoms of IEI are heterogeneous, and accurate diagnosis can be challenging and depends on the available human expertise and laboratory resources. The Middle East and North Africa (MENA) region has an increased prevalence of IEI because of the high rate of consanguinity with a predominance of autosomal recessive disorders. This area also exhibits more severe disease phenotypes compared with other regions, probably due to the delay in diagnosis. The MENA-IEI registry network has designed protocols and guidelines for the diagnosis and treatment of IEI, taking into consideration the variable regional expertise and resources. These guidelines are primarily meant to improve the care of patients within the region, but can also be followed in other regions with similar patient populations.

Effectiveness of Mesenchymal Stem Cell Therapy for COVID-19 Patients in the Intensive Care Unit: A Case-Control Study

Objective: Many methods are used in the treatment of coronavirus disease 2019 (COVID-19), which causes acute respiratory distress syndrome (ARDS), and there are conflicting reports in the literature regarding the results of mesenchymal stem cell (MSC) therapy, which is one of those methods. The aim of our study is to evaluate the effect of MSC treatment applied together with standard treatments on survival. Materials and Methods: This retrospective case-control study evaluates the survival effect of MSC treatment administered to patients treated in intensive care after the development of ARDS due to COVID-19 between March 2020 and March 2021. The age, gender, comorbid disease status, APACHE II score, and overall and comorbidity-based survival rates were compared between patients who received standard medical treatment (SMT) and patients who received MSC treatment together with SMT. Results: There were 62 patients in the group receiving only SMT and 81 patients in the group receiving SMT and MSC. No difference was observed between the groups in terms of age, gender, presence of comorbid diseases, or APACHE II scores. There were also no differences according to Kaplan-Maier analysis for the survival statuses of the groups. There was no serious adverse effect due to MSC treatment among these patients. Conclusion: Our study presents the largest case series in the literature, and it was observed that MSC treatment may not significantly affect overall survival or comorbid disease-based survival, in contrast to many other studies in the literature.

Comparing the levels of CTLA-4-dependent biological defects in patients with LRBA deficiency and CTLA-4 insufficiency.

BACKGROUND: Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency and cytotoxic T-lymphocyte protein-4 (CTLA-4) insufficiency are recently described disorders that present with susceptibility to infections, autoimmunity, and lymphoproliferation. Clinical and immunological comparisons of the diseases with long-term follow-up have not been previously reported. We sought to compare the clinical and laboratory manifestations of both diseases and investigate the role of flow cytometry in predicting the genetic defect in patients with LRBA deficiency and CTLA-4 insufficiency. METHODS: Patients were evaluated clinically with laboratory assessments for lymphocyte subsets, T follicular helper cells (TFH ), LRBA expression, and expression of CD25, FOXP3, and CTLA4 in regulatory T cells (Tregs) at baseline and 16 h post-stimulation. RESULTS: LRBA-deficient patients (n = 29) showed significantly early age of symptom onset, higher rates of pneumonia, autoimmunity, chronic diarrhea, and failure to thrive compared to CTLA-4 insufficiency (n = 12). In total, 29 patients received abatacept with favorable responses and the overall survival probability was not different between transplanted versus non-transplanted patients in LRBA deficiency. Meanwhile, higher probability of survival was observed in CTLA-4-insufficient patients (p = 0.04). The T-cell subsets showed more deviation to memory cells in CTLA-4-insufficiency, accompanied by low percentages of Treg and dysregulated cTFH cells response in both diseases. Cumulative numbers of autoimmunities positively correlated with cTFH frequencies. Baseline CTLA-4 expression was significantly diminished in LRBA deficiency and CTLA-4 insufficiency, but significant induction in CTLA-4 was observed after short-term T-cell stimulation in LRBA deficiency and controls, while this elevation was less in CTLA-4 insufficiency, allowing to differentiate this disease from LRBA deficiency with high sensitivity (87.5%) and specificity (90%). CONCLUSION: This cohort provided detailed clinical and laboratory comparisons for LRBA deficiency and CTLA-4 insufficiency. The flow cytometric approach is useful in predicting the defective gene; thus, targeted sequencing can be conducted to provide rapid diagnosis and treatment for these diseases impacting the CTLA-4 pathway.

Evaluation of the 10 Warning Signs in Primary and Secondary Immunodeficient Patients.

Objectives: Ten warning signs of primary immunodeficiency (PID) were suggested by the Jeffrey Modell Foundation (JMF), to increase physician awareness of PID. These warning signs have not yet been evaluated for patients with secondary immunodeficiency (SID). This study investigated whether the 10 warning signs used for the diagnosis of PID were also sufficient for the diagnosis of SID, and explored the possibility of additional signs. Methods: This prospective study was conducted between June and December 2020. The mothers of 162 patients with PID and SID, and mothers of 200 healthy children, were asked to complete a questionnaire about family and personal history in addition to the warning signs of PID developed by the JMF. A JMF score was created by giving one point for each "Yes" answer for the 10 warning signs of PID. Medical records of the patients were evaluated for possible additional warning signs for PID and SID. Results: The JMF scores of the PID (3.36 ± 1.65) and SID (3.72 ± 1.12) groups were significantly higher than the scores of the control group (0.34 ± 0.61) (p < 0.05). A sign for immunological evaluation in two patients without warning signs in the PID group was found to be chronic diarrhea. In addition to the 10 JMF warning signs, we found that consanguinity and a family history of tuberculosis were statistically significant in our PID group, compared with the SID and control groups. Conclusions: The JMF warning signs are important for early diagnosis of PID. Our study showed that these signs may also be used for the early diagnosis of SID in patients and, according to our results, in addition to the 10 JMF signs for PID, parental consanguinity, chronic diarrhea, and a family history of tuberculosis may also be considered warning signs for the early diagnosis of PID.

Memory B cells and serum immunoglobulins are associated with disease severity and mortality in patients with COVID-19.

PURPOSE OF THE STUDY: The aim of this study was to investigate the relationship of B cell-mediated immunity with disease severity and mortality in patients with COVID-19. STUDY DESIGN: In this retrospective cohort and single-centre study, 208 patients with laboratory-confirmed COVID-19 were recruited. A COVID-19 severity score, ranging from 0 to 10, was used to evaluate associations between various factors. Serum immunoglobulin levels and the number of cells in B lymphocyte subsets were measured and their association with disease severity and mortality in patients with COVID-19 examined. RESULTS: The median age of the patients was 50 (35-63) years and 88 (42%) were female. The number of deceased patients was 17. The median COVID-19 severity score was 8 (6-8) in deceased patients and 1 (0-2) in survivors. Deceased patients had significantly lower levels of total B lymphocytes, naive B cells, switched memory B cells, and serum IgA, IgG, IgG1 and IgG2 than recovered patients (all p<0.05). In addition, a significant negative correlation was found between the number of these parameters and COVID-19 severity scores. Decrease in the number of total B cells and switched memory B cells as well as lower serum IgA, IgG and IgG1 levels were independent risk factors for mortality in patients with COVID-19. CONCLUSION: In the present study, the prognosis of patients with COVID-19 was shown to be associated with the B cell subset and serum immunoglobulin levels.

Evaluation of immunological abnormalities in patients with rare syndromes.

Introduction: Recurrent infections are important problems in syndromic patients. This study aimed to evaluate immunological abnormalities in patients who presented with recurrent infections and were diagnosed with rare syndromes. Material and methods: This retrospective analysis included 14 patients with complaints of recurrent infections, all of whom were diagnosed with a rare syndrome. Results: The study group consisted of patients with Aicardi syndrome, Brugada syndrome, Phelan- McDermid syndrome, trichothiodystrophy, LEOPARD syndrome, Prader-Willi syndrome, Seckel syndrome, trisomy 18 (Edwards' syndrome), Wiedemann-Steiner syndrome, West syndrome, Williams syndrome, 47,XYY syndrome, 16p13 deletion syndrome, and 13q1.3 deletion syndrome. Seven patients (50%) were girls and seven (50%) were boys (mean age, 56.7 ±32.9 months; median [range] age: 45.5 [27-153] months). There were high rates of consanguinity (50%), cesarean section delivery (71%), and hospitalization in the intensive care unit (78.5%). No patients had a family history of immunodeficiency. On admission, all patients exhibited humoral and/or cellular immune system abnormalities. During the follow-up period, all T-cell abnormalities were improved after immunoglobulin replacement therapy (IGRT), while B-cell abnormalities persisted. These findings suggested that the patients predominantly had antibody deficiencies associated with mild T-cell abnormalities because of recurrent infections. The rates of infections and hospitalizations were significantly reduced after IGRT (p < 0.001); the rate of intensive care unit admission also significantly decreased (from 78.5% to 21.4%). Two of the three oxygen-dependent patients exhibited improvement therein. IGRT was discontinued in two patients with significant clinical improvement during follow-up. Conclusions: An immunological evaluation should be considered in pediatric patients with rare syndromes and recurrent infections. IGRT may help to improve the prognoses of these patients.

STK4 deficiency and EBV-associated lymphoproliferative disorders, emphasis on histomorphology, and review of literature.

Aberrations of the STK4 gene in humans result in an autosomal recessively inherited primary immunodeficiency. We identified three patients with STK4 deficiency who had presented to our hospital and reviewed their biopsy samples with the goal of detailing the characteristics of STK4 deficiency from a pathology perspective. Case 1 was a 20-year-old male who presented with cervical and supraclavicular lymphadenopathy which showed plasmacytic hyperplasia and a concurrent bronchial mass, with AA amyloidosis and EBV-associated "polymorphic lymphoproliferative disorder (LPD) resembling polymorphic post-transplant LPD." The second case was an 8-year-old girl with abdominal lymphadenopathy; biopsy revealed a complex lymphoproliferation which consisted of EBV-associated "polymorphic LPD resembling polymorphic post-transplant LPD," plasmacytic hyperplasia, granulomatous reaction, and a CD4- and PD-1-positive clonal T cell proliferation. The third was a 15-year-old girl with a laryngeal mass, representing a high-grade B cell lymphoma with prominent plasmacytic differentiation. Our cases emphasize the complex and challenging histopathology of lymphoid proliferations in patients with STK4 deficiency.

Long-Term Experience of Subcutaneous Immunoglobulin Therapy in Pediatric Primary Immunodeficient Patients with Low and Normal Body Weight.

PURPOSE: The aim was to review the compliance, side effects and effectiveness of subcutaneous immunoglobulin (SCIG) supplementation in patients with primary immunodeficiencies (PID) who had previously received intravenous immunoglobulin (IVIG) therapy and subsequently switched to SCIG, as well as to compare these parameters in patients while considering body weight. METHODS: Demographic data, clinical and laboratory findings, SCIG dose, and side effects of 87 patients were retrospectively obtained from patient files. In patients who first received IVIG and then SCIG, the monthly SCIG dose was calculated by multiplying the IVIG dose by 1.37. The total monthly SCIG dose was distributed via injection across three or four doses per month, thus every 7 or 10 days. RESULTS: Of the 87 patients aged between one and 22 years, 50 were male (57.5%) and 37 were female (42.5%). The serum IgG levels of the SCIG group were higher and more stable than those of the IVIG group. The number of hospitalizations and infections decreased significantly after initiation of SCIG. Thirteen patients (14.9%) had low body weight (LBW) for their age, seven of whom were male (53.8%). Serum IgG levels of the LBW cohort were significantly elevated and more stable during the SCIG period than the IVIG period. Mild, local side effects were detected in 153 administrations (3.3%) in 30 patients with normal body weight, while no local reactions were recorded in the patients with LBW. CONCLUSION: SCIG supplementation is an effective treatment for pediatric patients with PID. The preliminary data from the present study suggest that such treatment is also safe for LBW children. The numbers of patient hospitalizations and family visits to clinics were reduced, allowing our patients and their parents to live more normal lives.

Primary antibody deficiencies in Turkey: molecular and clinical aspects.

Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n = 4), CD40L (n = 1), ICOS (n = 1), IGHM (n = 1), and TCF3 (n = 1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2-10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.