Investigating serum free light chains in patients with common variable immunodeficiency disorder in compare with other immunodeficiency diseases.

Immune-related enteropathies (IREs) represent a heterogeneous group of disorders characterised by immune-mediated small bowel injury. While coeliac disease is the most common cause, widespread use of small bowel endoscopy has expanded the recognition of rarer causes. This review aims to summarise recent advances in diagnosis, classification and management of IRE. Significant overlap exists between coeliac disease, autoimmune enteropathy, collagenous sprue, drug-induced enteropathies, common variable immunodeficiency (CVID) associated enteropathy and other IRE. A recent meta-analysis supports a no-biopsy approach in selected adults with significantly elevated IgA tissue transglutaminase levels and suspected coeliac disease. Refractory coeliac disease type II is now recognised as a low-grade intraepithelial T-cell lymphoma with a high risk of progression to enteropathy-associated T-cell lymphoma (EATL). Drug-induced enteropathies, particularly olmesartan-associated enteropathy, are increasingly detected and may mimic autoimmune enteropathy histologically. Novel therapeutic approaches, including cladribine, JAK inhibitors and biologics, have shown promise in refractory disease, although evidence is limited to small studies. IREs present substantial diagnostic and therapeutic challenges due to overlapping characteristics and variable disease course. A structured approach integrating clinical, serological and histopathological data is essential for accurate diagnosis. Early recognition and tailored management are crucial to prevent long-term complications.

Aims: This study investigated whether baseline serum IgG4-to-IgG ratios are associated with the presence of autoimmune manifestations in patients diagnosed with common variable immunodeficiency (CVID). Methods: A retrospective cohort analysis was performed using clinical data from 85 patients with CVID evaluated between January 2013 and November 2023. The study included patients aged 18 years and over with a confirmed diagnosis of CVID. Patients with incomplete or insufficient clinical information were excluded. Serum IgG4-to-IgG ratios measured at initial assessment were compared between individuals with autoimmune manifestations and those without. Results: Of the 85 patients, 36 (42.4%) had at least one autoimmune condition. Autoimmune cytopenias constituted the most frequent autoimmune presentation (17.6%). The median IgG4-to-IgG ratio in CVID with autoimmune disease was 0.018 (interquartile range, 0.014–0.043), which was significantly lower than that observed in the group without autoimmunity (p=0.03). Building on this finding, ROC analysis identified a threshold IgG4-to-IgG ratio of 0.04 for differentiating autoimmune from non autoimmune cases (AUC 0.709; 95% CI 0.60–0.82; p=0.002; sensitivity 72%; specificity 60%). Finally, logistic regression analysis demonstrated that a reduced IgG4-to-IgG ratio was significantly associated with the development of autoimmune disease (odds ratio, 1.682; 95% confidence interval, 1.129–2.489; p=0.037). Conclusion: Lower baseline IgG4-to-IgG ratios were associated with autoimmune manifestations in CVID. This parameter may serve as a practical adjunctive biomarker for the early identification and monitoring of autoimmune complications in this heterogeneous disorder.

Background: Common variable immunodeficiency (CVID) is the most frequent symptomatic primary antibody deficiency, associated with recurrent infections, immune dysregulation, and non-infectious complications. Amyloidosis is a rare but severe complication with pulmonary involvement being exceptional. Objective: The aim of this study was to review reported cases of amyloidosis complicating CVID and present a unique case of pulmonary involvement. Methods: A literature research identified observational studies and case reports linking amyloidosis with CVID. Additionally, we describe a patient with CVID complicated by pulmonary and gastrointestinal amyloidosis. Results: Fifteen cases were identified, mostly amyloid A (AA) with multiple organ involvement. Only one case of pulmonary amyloidosis was reported. To date, no cases of pulmonary light-chain amyloidosis (AL) have been described in CVID patients without an underlying plasma cell dyscrasia. Our patient initially presented with AA amyloidosis but evolved to systemic AL type with rapid progression and fatal outcome despite therapy. Conclusions: Amyloidosis should be considered in CVID patients with atypical symptoms. Accurate amyloid typing is essential as treatment differs between AA and AL types. Early recognition may improve outcomes.

Inborn errors of immunity (IEI), formerly referred to as primary immunodeficiency disorders, comprise ten groups and more than 500 distinct diseases. Common variable immunodeficiency (CVID) is the most prevalent symptomatic IEI in adults and is characterised by reduced immunoglobulin levels and recurrent infections after exclusion of secondary causes of hypogammaglobulinaemia. Granulomatous lymphocytic interstitial lung disease (GLILD) is a distinct clinical entity associated with CVID, defined by lymphoid proliferation and granuloma formation within the lung interstitium. GLILD shares numerous clinical, radiological, and pathological similarities with sarcoidosis; however, hypogammaglobulinaemia, indicative of immunodeficiency, is rarely encountered in sarcoidosis. To present a case initially diagnosed as sarcoidosis, in whom hypogammaglobulinaemia detected during follow-up led to the final diagnosis of primary immunodeficiency with granulomatous lymphocytic interstitial lung disease. This case report retrospectively reviews the patient’s clinical course, laboratory data, radiological findings, and histopathological results. Following the detection of hypogammaglobulinaemia, comprehensive immunological evaluation was performed, confirming the diagnosis of primary immunodeficiency. GLILD can closely mimic sarcoidosis in clinical, radiological, and pathological aspects. The presence of hypogammaglobulinaemia should prompt consideration of underlying primary immunodeficiency. This case highlights the importance of immunological assessment in patients with granulomatous interstitial lung disease to ensure accurate diagnosis and appropriate management.

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency or inborn error of immunity (IEI) encountered in clinical practice. Characterized by a remarkably broad clinical spectrum, CVID presents with phenotypes spanning from "infection only" to significant non-infectious complications. The frequent overlap between these classifications underscores that their distinction is more accurately viewed as a continuous spectrum, rather than a binary categorization. CVID-associated liver disease is a significant source of morbidity, yet often poses diagnostic challenges due to its insidious and clinically silent nature, typically becoming apparent only upon the development of complications. Manifestations range from abnormal liver tests to irreversible organ damage, with reports including granulomas, autoimmune hepatitis, fibrosis, and porto-sinusoidal vascular disorder (PSVD). Regenerative nodular hyperplasia (RNH), commonly associated with PSVD, is a frequent histopathological finding. Management requires a multidisciplinary approach, including cause-directed immunosuppression and supportive treatment for non-cirrhotic portal hypertension. Despite significant advances in comprehending CVID-associated liver involvement, substantial gaps persist concerning its pathogenesis, its optimal management, and the correlation between histological findings and clinical outcomes. A heightened awareness of CVID-associated liver disease is paramount for multidisciplinary teams across IEI centers. Furthermore, given its prevalence, its insidious clinical phenotype until advanced complications, and the significant diagnostic delay and underdiagnosis, such awareness is critical across a broader range of medical specialties. In this paper, we aim to consolidate current knowledge regarding CVID-related liver disease, examining its clinical presentation, recent genetic and pathogenetic advancements along with current diagnostic methodologies, and therapeutic strategies.

Up to one-third of the patients diagnosed with common variable immunodeficiency (CVID) may develop gastrointestinal (GI) and hepatic manifestations. This study aimed to evaluate the prognostic significance of enteropathy and liver disease in patients with CVID. We conducted a retrospective study including all consecutive adult patients with CVID followed in a tertiary care center in Spain from January 1990 to January 2023. A diagnosis of CVID-associated enteropathy (CVID-E) and CVID-associated liver involvement (CVID-L) was established when objective clinical, endoscopic, histologic, radiologic or hemodynamic findings were present. Relevant prognostic outcomes and their risk factors were studied, including survival, GI infections, and GI cancer. Eighty-nine patients with confirmed CVID were included, 26 of them (29.2%) had CVID-E and 23 (25.8%) had CVID-L. Nineteen (73.1%) patients with CVID-E suffered from GI infections, while 12 (46.2%) presented concurrent liver involvement. In comparison with the rest of the cohort, patients with CVID-E had more frequently liver involvement, GI infections, and GI cancer. Multivariate analysis identified CVID-E as an independent risk factor for GI infections. Twelve (52.2%) patients with CVID-L concurrently exhibited CVID-E, and patients with CVID-L presented more CVID-E, splenomegaly, and a trend toward more GI cancer and GI infections. CVID-L and age at CVID diagnosis emerged as independent risk factors for mortality. GI and hepatic involvements are common in patients with CVID and frequently occur together. These manifestations significantly affect the disease course, increasing the risk of GI infections, GI malignancy, and, in the case of liver disease, mortality.

Anesthesia Management of a Patient With Common Variable Immunodeficiency and End-stage Liver Disease Undergoing Laparoscopic Surgery: A Case Report.

Fasciitis-like primary breast pyoderma gangrenosum: A rare case report

Immunoglobulin replacement therapy (IRT) for primary immunodeficiency reduces infection risk and subsequent complications and can be lifesaving. However, IRT can cause severe systemic adverse events (AEs) that may limit adequate dosing. These AEs may be caused, in part, by activation and/or consumption of complement proteins, thereby lowering C1 esterase inhibitor (C1-INH) levels. Data suggest that C1-INH administration prior to intravenous immunoglobulin (IVIG) may reduce IVIG-related AEs. This case describes an adult with common variable immunodeficiency unable to tolerate IRT therapy (subcutaneous immunoglobulin [SCIG] 20% solution once weekly). She experienced AEs of severe neuropathy, described as burning and pins-and-needles sensation in the extremities and muscle twitching for several days post-treatment. Dose decreases of SCIG to 0.5 g did not improve the AE profile. Inability to tolerate IRT caused suboptimal dosing and inadequate primary immunodeficiency management, resulting in hospitalizations for pneumonia and sepsis. A trial of recombinant human C1-INH 4200 U was administered intravenously over approximately 5 min, 1 h prior to SCIG 1 g (Day 1). This dose was well tolerated with minimal AEs reported. SCIG 3 g was administered on Days 2 and 3 with no AEs reported. By continuing routine recombinant human C1-INH 4200 U prophylaxis, the patient was able to tolerate the recommended dose of SCIG 20 g once weekly without the debilitating neuropathy and other AEs previously experienced with SCIG alone. This case suggests that a patient with IRT-related AEs may benefit from C1-INH replacement therapy prior to SCIG/IVIG administration to improve tolerability.

Common Variable Immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in adults. While infections are common, over 50% of patients exhibit autoimmune and immune activation related complications. Chronic inflammation from dysbiosis may affect the heart in CVID, though its relationship with gut barrier and echocardiographic findings is still unclear. This study investigates the associations between intestinal permeability, Trimethylamine N-oxide (TMAO) levels, immune activation, and cardiac function in CVID patients. The study included 31 CVID patients and 31 matched healthy controls. Serum zonulin, TMAO, soluble CD14 (sCD14), soluble CD25 (sCD25), Tumor Necrosis Factor-alpha (TNF-α), and IL-17 A levels were measured by ELISA. Cardiac function was assessed using speckle-tracking echocardiography (STE), focusing on global longitudinal strain (GLS). Increased levels of zonulin and TMAO were observed in CVID patients. sCD14 and sCD25 levels correlated strongly with TMAO. TMAO showed a negative correlation with Ejection Fraction and a positive correlation with Pulmonary Artery Pressure (PAP). No significant differences were found in serum TNF-α and IL-17 A levels in the compared groups. Compared to the control group (-19.90 ± 2.41), a remarkable reduction in mean GLS (-18.13 ± 3.13) was determined in the CVID group. These results are early indicators of myocardial dysfunction. Strain analysis showed a significant decrease in negative Apical 4-Chamber View Basal Longitudinal Strain (AP4B) and Apical 3-Chamber View Basal Longitudinal Strain AP3B values in the CVID group (p = 0.012 and p = 0.027). In this study, elevated serum zonulin and TMAO levels correlated with increased intestinal permeability and immune activation in CVID. High TMAO was linked to early myocardial dysfunction, highlighting the potential of microbiome-targeted therapies and advanced echocardiography for early cardiac risk detection in CVID.

Primary immunodeficiencies (PIDs) are rare disorders caused by immune system defects that are commonly screened using multi-parameter flow cytometry (FCM). To counter the subjective and time-consuming manual data analysis of FCM data, we present PIDgeon, a fully automated computational pipeline based on artificial intelligence (AI) techniques. PIDgeon is designed to characterize PID immune profiles, suggest PID subtypes based on altered immune profiles, age, and immunoglobulin levels, and generate interpretable reports. The PIDgeon pipeline, including FlowSOM and extreme gradient boosting models, was trained and tested on standardized FCM data generated according to EuroFlow procedures on 74 healthy controls and 399 patients (281 lymphoid-PID patients and 118 non-PID diseased controls) collected by the Ghent University Hospital. Subsequently, multi-centric validation was performed on internal (n = 211) and external (n = 338) independent data sets collected across 4 EuroFlow centers. Validation demonstrated high accuracy in cell count enumeration, achieving correlation scores above 0.90 for the major lymphocyte subsets. Interestingly, PIDgeon showed high sensitivity (93% to 100%) in predicting PID with severe T-cell defects, such as severe combined immunodeficiency and late-onset combined immunodeficiency, and low false-negative rates (1.5% to 5.4%) for distinguishing other lymphoid-PID vs non-PID diseased controls across data sets. Additionally, PIDgeon gives a first hint toward prediction of subtypes of primary antibody deficiencies, such as common variable immunodeficiency. In summary, PIDgeon is an accessible and explainable AI-pipeline aligned with current clinical needs, aiding laboratory immunologists in early PID diagnostics and increasing data analysis efficiency.

Common variable immunodeficiency disorder (CVID) is the most prevalent primary immunodeficiency in adults. Pathogenic mutations of the TNFRSF13B gene were identified in CVID patients and associated with autoimmunity and lymphoproliferation. A study on Swedish children unaffected by CVID has shown that rare variants in the TNFRSF13B gene increase the risk of asthma. To the best of our knowledge, asthma has not been reported in CVID patients with TNFRSF13B gene mutations. We described a patient suffering from asthma and CVID with a heterozygous mutation in the TNFRSF13B gene. According to our findings and previous studies, mutations in the TNFRSF13B gene seem to be possibly associated with the occurrence of asthma in CVID patients.

Regulation of gene expression is central to the development of immune cells and their ability to respond to infection. As part of a clinical evaluation, we identified two sisters with recurrent infections, hypogammaglobulinemia, and memory B cell deficiency, diagnosed as common variable immunodeficiency. Whole exome sequencing identified a heterozygous variant (Leu50Ser, L50S) in a conserved region of EZH2, the catalytic subunit of the epigenetic gene repressor Polycomb Repressive Complex 2 (PRC2). EZH2-catalyzed histone H3 lysine 27 methylation (H3K27me) in bulk was not overall significantly disrupted by this variant, in patient samples or cell lines expressing EZH2-L50S. EZH2-L50S protein is expressed similar to wild-type and can form PRC2. However, we find that specific genomic regions that normally have high wild-type levels of H3K27me3 are deficient in the L50S context, particularly around gene promoters. EZH2-L50S is still recruited to these sites, but is not as active. Using recombinant purified PRC2, we determine that L50S affects methylation of nucleosomes and disrupts allosteric stimulation that normally amplifies H3K27me3, consistent with the location of L50 in the allosteric regulatory region of PRC2. Thus, variation of EZH2 L50, occurring at low frequency in the population may interfere with normal B cell gene expression patterns, contributing to immunodeficiency. This study has implications for genetic variation in PRC2 in the general population.

Background: Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency in adults, characterized by reduced serum immunoglobulin levels and impaired specific antibody responses. While immunoglobulin replacement therapy improves infection control, it has limited impact on phenotypic complications such as autoimmunity, polyclonal lymphoproliferation, enteropathy, and cytopenias, which may substantially affect patients’ quality of life (QoL). This study aimed to evaluate the relationship between distinct clinical phenotypes of CVID and QoL using the disease-specific CVID-QoL questionnaire. Materials and methods: This cross-sectional study included 30 adult CVID patients followed at the Immunology Clinic of Erciyes University Faculty of Medicine, diagnosed according to European Society for Immunodeficiencies criteria, and receiving regular intravenous immunoglobulin therapy. Demographic and clinical data were obtained retrospectively from medical records. Patients were classified into clinical phenotypes—uncomplicated, cytopenia, polyclonal lymphocytic inflammation (PLI), and enteropathy—based on dominant presentation at diagnosis. QoL was assessed using the CVID-QoL, which evaluates emotional functioning (EF), relational functioning (RF), and gastrointestinal/skin symptoms (GSS). Statistical analyses compared QoL scores across phenotypes. Results: The cohort comprised 16 females (53.3%) and 14 males (46.7%), with a mean age of 36.1 ± 11.2 years and a mean diagnostic delay of 11.7 ± 9.7 years. The most common phenotype was PLI (46.6%), followed by uncomplicated (36.6%), cytopenia (23.3%), and enteropathy (16.6%). Seven patients (23.3%) had 2 phenotypes simultaneously. Enteropathy phenotype was associated with significantly higher GSS scores ( P = 0.020). Patients with 2 phenotypes had significantly worse total CVID-QoL, EF, and GSS scores ( P = 0.006, 0.003, and 0.002, respectively), while RF scores were unaffected. Conclusion: Clinical phenotypes in CVID influence QoL to varying extents, with enteropathy and multiple concurrent phenotypes showing the greatest negative impact. These findings highlight the need for phenotype-based monitoring and targeted interventions to address both infection control and broader QoL determinants in CVID management.

Common variable immunodeficiency (CVID) is a primary antibody defect that leads to frequent infections, but inflammatory complications appear in 30-50%, leading to increased morbidity and mortality. We have previously shown that circulating bacterial 16S ribosomal DNA (rDNA), originating from gut commensals, is significantly increased in the serum of patients with CVID with inflammatory conditions (P = 0.0007). Here we examined the relationships between serum 16S ribosomal DNA (rDNA), isotype-switched memory (SM) B cells, serum IgA, IgA+ SM B cells, serum IFN-γ, and serum B cell-activating factor (BAFF). We found a significant inverse correlation between serum 16S ribosomal DNA (rDNA) concentrations and the numbers of isotype SM B cells, IgA+ SM B cells, and serum IgA levels in our large cohort, suggesting that loss of IgA in the mucosal barrier permits bacterial transcytosis. Loss of SM B cells and lower serum IgA concentrations were both associated with increased serum IFN-γ, as well as increased CXCL9 and serum BAFF concentrations. Serum BAFF was also significantly associated with IFN-γ levels and inversely correlated with baseline serum IgA. We conclude that loss of IgA, accompanied by mucosal defects in CVID, may permit bacterial transcytosis, resulting in excessive IFN-γ and BAFF production, both of which promote autoimmune and inflammatory complications in this immune defect.

PurposeThe impact of coronavirus disease 2019 (COVID-19) on patients with primary immunodeficiency (PID) remains insufficiently characterized. This study aimed to describe the clinical manifestations, disease course, and outcomes of COVID-19 in patients with PID.MethodsAdult patients with PID who had COVID-19 infection between March 2020 and August 2022 were screened. Demographic and clinical data were retrospectively collected from institutional databases, and additional information was obtained through a patient questionnaire.ResultsA total of 36 patients (19 males, 17 females; median age: 36.5 years) with various PID subtypes were included: 24 with common variable immunodeficiency (CVID), 3 with cytotoxic T-lymphocyte-associated protein-4 haploinsufficiency, 3 with X-linked agammaglobulinemia (XLA), 2 with hypogammaglobulinemia, 1 with lipopolysaccharide-responsive and beige-like anchor protein deficiency, 1 with DiGeorge syndrome, 1 with mitochondrial neurogastrointestinal encephalomyopathy syndrome, and 1 with CVID-like capillary malformation-arteriovenous malformation syndrome 2. Overall, 63.9% (n = 23) were managed as outpatients, while 36.1% (n = 13) required hospitalization. Admission to the intensive care unit was required in 19.4% (n = 7) of the cases. The overall case fatality rate was 8.3% (n = 3), which is higher than the rate observed in the general population. Although the majority experienced a mild clinical course, patients with XLA exhibited prolonged symptoms and persistent seropositivity. Risk factors associated with hospitalization included lymphopenia, elevated C-reactive protein and ferritin levels, dyspnea, COVID-19 Reporting and Data System score ≥ 4 on imaging, need for supplemental oxygen, prolonged symptoms, and extended polymerase chain reaction positivity.ConclusionsA subset of adult patients with PID may be at increased risk for severe COVID-19.

This study aimed to determine the frequency of neutropenia in patients with common variable immunodeficiency (CVID) and investigate its relationship with disease prognosis. Data from 84 patients diagnosed with CVID and followed between 2019 and 2024 at the Department of Adult Clinical Immunology and Allergy, Necmettin Erbakan University, were retrospectively reviewed. Patients were divided into two groups based on the presence or absence of neutropenia. Demographic data, clinical findings, laboratory parameters, and survival rates were compared. Statistical analyses included the Mann-Whitney U test, the Chi-square test, and the Kaplan-Meier survival analysis. A total of 84 patients diagnosed with CVID were included in the study, with a median age of 38 years (range, 20-79 years). Of the participants, 48.8% were females (n = 41). Neutropenia was observed in 28.5% of patients (n = 24). The most common presenting complaints included autoimmune cytopenias, such as anemia and thrombocytopenia. Compared to non-neutropenic patients (n = 60), those with neutropenic CVID had a significantly higher mortality rate (33.3% vs 6.7%, P = 0.004). According to Kaplan-Meier survival analysis, the 8-year survival rates were 57.5 and 92.5% for neutropenic and for non-neutropenic CVID patients (p < 0.001), respectively. This study suggests that neutropenia in CVID patients may be more than just a hematological issue; it could also serve as an important clinical marker associated with increased mortality. Recognizing and closely monitoring neutropenia is essential for effective CVID management.

Common variable immunodeficiency (CVID) is one of the primary immunodeficiency disorders. The phenotype of peripheral blood memory B cells is a useful tool in the classification of patients into clinically and functionally relevant groups. This study aimed to assess the level of naïve and switched memory B cells level and their correlation with the clinical phenotypes and complications in patients with CVID. This case control study included 30 adult patients with CVID and 30 normal controls, matched for age and sex. Complete blood count, cluster of differentiation 3 (CD3)+, CD4+, CD8+ T cells and CD19+27-IgD+ for naïve B cells and CD19+27+IgD- switched memory B cells levels were assessed. The mean age of the onset of symptoms was 16.9±15.1 years, the mean age of diagnosis was 27.30±14.39 years, with a diagnostic delay of 10.43±10.29 years, and the body mass index was significantly lower in CVID group. Infections including (upper respiratory tract infection, chronic diarrhea, pneumonia and bronchiectasis) were the most frequent phenotypes. CD4+, CD4+/CD8+ T cells, CD19+ and CD19+27+IgD- switch memory B cell, IgG, IgA, and IgM were significantly lower in CVID group than in the control group (p < 0.001 and p < 0.015, respectively). CD8+ T cells and CD19+27-IgD+ naïve B cells were significantly higher in the CVID group (p < 0.001). CD19+27-IgD+ naïve B cells level was significantly lower in cases with bronchiectasis with low baseline serum IgG in lymphadenopathy group (p=0.049), and higher level of CD3+ T cells in cases with splenomegaly. There was no significant difference in laboratory results in CVID patients presented with autoimmune diseases, Granulomas nor enteropathy. In conclusion, high level of CD19+27-IgD+ naïve and low level of CD19+27+IgD- switch memory B cells are characteristic features of CVID. Moreover, the reduced CD19+27-IgD+ naïve B cells level can be a predictor of the development of bronchiectasis in CVID patients.

Common variable immunodeficiency (CVID) is a primary antibody deficiency characterized by hypogammaglobulinemia and recurrent infections. Studies on the effects of CVID in pregnant patients are still needed. We aimed to investigate the effects of CVID on pregnancy outcomes and newborns. We retrospectively evaluated 33 women with CVID and 94 pregnant women at our center. Patients were assessed based on infection rates, pregnancy complications, and use of immunoglobulin replacement therapy (IgRT) in both preterm and post-term periods. Patient data were collected from hospital databases and medical records. The mean age at first pregnancy was 24.7 (17-45) years, with an average of 2.8 pregnancies per woman. CVID was detected before pregnancy in 24.2% of cases, and 24.2% of patients initiated IgRT during pregnancy. The live birth rate was 69.1%, while early fetal loss occurred in 27.7% of pregnancies, and stillbirth in 3.2%. Infection-related complications occurred in 18% of pregnancies and 14.9% of postpartum periods. The most common infections were upper respiratory and urinary tract infections. Parenteral antibiotic treatment was required for patients who did not receive IgRT during pregnancy. Neonatal infections were observed in 6.6% of cases, and the admission rate to the neonatal intensive care unit was 5.5%. Our study emphasizes that live birth and fetal loss rates in patients with CVID are comparable to those in the general population. Informing patients of the potential risks associated with consanguinity is crucial. Moreover, given the increased vulnerability of patients with CVID to infections, extra precautions are needed during pregnancy and the postpartum period.