Hypogammaglobulinemia

BACKGROUND: Biallelic pathogenic variants in SLC5A6 resulting in sodium-dependent multivitamin transporter (SMVT) defect have recently been described as a vitamin-responsive inborn error of metabolism mimicking biotinidase deficiency. To our knowledge, only 16 patients have been reported so far with various clinical phenotypes such as neuropathy and other neurologic impairments, gastro-intestinal dysfunction and failure to thrive, osteopenia, immunodeficiency, metabolic acidosis, hypoglycemia, and recently severe cardiac symptoms...

B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥ 3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively)...

Ataxia telangiectasia (A-T), caused by biallelic variants in the ATM gene, is a multisystemic and severe syndrome characterized by progressive ataxia, telangiectasia, hyperkinesia, immunodeficiency, increased risk of malignancy, and typically death before the age of 30. In this retrospective study we describe the phenotype of 14 pediatric and adult A-T patients evaluated at the Karolinska University Hospital in Sweden during the last 12 years. Most of the patients in this cohort were severely affected by ataxia and wheelchair use started at a median age of 9 years...

Common variable immunodeficiency (CVID) is the most frequent form of primary hypogammaglobulinemia in adults. In addition to recurrent infections and respiratory manifestations, CVID patients may present several non-infection complications such as autoimmune diseases. The mechanisms that lead to immune dysregulation in CVID are not completely understood. Given the role of IgD on naïve B cells in the maintenance of tolerance and secreted IgD in the respiratory mucosa, we evaluated the frequency of IgD+ naïve and IgD+ memory B cells in CVID patients...

Good Syndrome is a rare disease that comprises the presence of a thymoma, immunodeficiency, and recurrent opportunistic infections. We report the case of a young woman who was diagnosed with Good Syndrome, who had a long-term history of recurrent infections, often due to atypical agents, and who also had a previous history of immunodeficiency and a B1 thymoma invading the large vessels, lung, and pericardium (Masaoka stage IV). She underwent surgical resection of the mediastinal mass, requiring vena cava superior reconstruction due to the extent of invasion, followed by adjuvant radiotherapy and immunoglobulin G supplementation...

BACKGROUND: Ocrelizumab is an effective anti-CD20 therapy approved for Relapsing Remitting (RRMS) and Primary Progressive Multiple Sclerosis (PPMS). In clinical trials, a proportion of patients developed hypogammaglobulinemia which could contribute to infection risk. This study aimed to identify hypogammaglobulinemia and its risk factors and evaluate potentially associated serious infection risk in a real-world cohort of patients. METHODS: All MS patients treated with ocrelizumab in a Quebec City MS clinic from January 2017 to August 2021 were included and detailed patient characteristics were collected by chart review...

Post-coronavirus disease 2019 (post-COVID-19) condition is a post-acute syndrome characterized by non-specific symptoms that remain for at least two months and typically appear three months after the start of the acute phase. Individuals with chronic lymphocytic leukemia (CLL) are considered to be at high risk of contracting COVID-19. It is also becoming increasingly evident that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response is frequently lacking or insufficient. We present a 77-year-old male patient with CLL who had multiple hospitalizations for the management of pneumonia related to persistent COVID-19 infection due to hypogammaglobulinemia...

CLL is associated with an increased risk of infectious complications. Treatment with BTK or BCL-2 inhibitors does not seem to increase significantly the risk of opportunistic infections, but the role of combination therapies including BTK and/or BCL-2 inhibitors remains to be established. Various infectious complications can be successfully prevented with appropriate risk management strategies. In this paper we reviewed the international guidelines on prevention and management of infectious complications in patients with CLL treated with BTK or BCL-2 inhibitors...

Objective: To investigate the incidence and influencing factors of hypogammaglobulinemia (HGG) in children with steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) treated with rituximab (RTX), and its relationship with the risk of severe infections. Methods: The clinical data of children with SDNS/FRNS treated with RTX at the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University from December 2020 to January 2023 were retrospectively analyzed. RTX treatment was performed using a B-cell-guided regimen (a single dose of 375 mg/m2 , a maximum of 500 mg/dose, and an additional one dose when reassessment of peripheral blood CD19+ B cells≥1%)...

BACKGROUND: While primary intestinal lymphangiectasia (PIL) is considered a rare condition, there have been several reported cases in adults. Nevertheless, the absence of clear guidance from diagnosis to treatment and prognosis poses challenges for both physicians and patients. AIM: To enhance understanding by investigating clinical presentation, diagnosis, treatment, complications, and prognoses in adult PIL cases. METHODS: We enrolled adult patients diagnosed with PIL between March 2016 and September 2021...

Selective IgA deficiency (sIgAD) and Common Variable Immunodeficiency (CVID) and Transient Hypogammaglobulinemia of Infancy (THI) are the most frequent forms of primary antibody deficiencies. Difficulties in initial diagnosis, especially in the early childhood, the familiar occurrence of these diseases, as well as the possibility of progression to each other suggest common cellular and molecular patomechanism and a similar genetic background. In this review, we discuss both similarities and differences of these three humoral immunodeficiencies, focusing on current and novel therapeutic approaches...

Congenital Myotonic Dystrophy (CMD) is an autosomal dominant hereditary disease caused by mutations in the dystrophia myotonica protein kinase gene. Patients with CMD often exhibit low immunoglobulin (Ig) G levels. While Ig replacement therapy for low IgG levels has been reported in several adult cases, there have been no reports on pediatric patients. This study presents a first pediatric case where Ig replacement therapy effectively eliminated susceptibility to infections. The CMD patient, a 1-year-old Japanese female with a history of premature birth and necrotizing enterocolitis, developed recurrent severe bacterial infections due to hypogammaglobulinemia...

The term common variable immunodeficiency (CVID) encompasses a clinically diverse group of disorders, mainly characterized by hypogammaglobulinemia, insufficient specific antibody production, and recurrent infections. The genetics of CVID is complex, and monogenic defects account for only a portion of cases, typically <30%. Other proposed mechanisms include digenic, oligogenic, or polygenic inheritance and epigenetic dysregulation. In this study, we aimed to assess the role of skewed X-chromosome inactivation (XCI) in CVID...

Chronic Lymphocytic Leukemia (CLL) is well-known for increasing susceptibility to infections. Factors such as immune dysregulation, IGHV status, hypogammaglobulinemia, and patient comorbidity and treatment, contribute to higher infection rates and mortality. However, the impact of hypogammaglobulinemia on infection rates is controversial. We aimed to identify clinical and biological parameters linked to the risk of severe infectious events. Additionally, we set up a straightforward risk infection score to stratify CLL patients at diagnosis, thereby enabling the development of suitable infection prevention strategies...

No abstract text is available yet for this article.

INTRODUCTION: X-linked lymphoproliferative syndrome (XLP) is a rare primary immune deficiency. Two types of XLP have been described: XLP-1 and XLP-2. METHODS: We found 7 patients with XLP (3 had XLP-1 and 4 had XLP-2) after reviewing the data from Pediatric Immunodeficiency Clinic from 1997 to 2021. RESULTS: Mean age at diagnosis was 3.8 years, and mean delay in diagnosis was 2.6 years. Five patients had recurrent episodes of infections. Four patients developed at least one episode of hemophagocytic lymphohistiocytosis (HLH) (2 with XLP-1 and 2 with XLP-2)...

Thymoma with Immunodeficiency (Good's Syndrome, GS) is a rare association between thymoma and immunodeficiency, first described over 60 years ago. Patients with GS typically present with thymomas, reduced or absent B cells in the peripheral blood, hypogammaglobulinemia, and defects in cell-mediated immunity. We report the case of a 67-year-old woman diagnosed with GS following the development of a progressive, severe, refractory pulmonary infection and diffuse panbronchiolitis (DPB). She also had diabetes, characterized by anti-glutamic acid decarboxylase antibody positivity, leading to a diagnosis of latent autoimmune diabetes in adults (LADA)...

Good Syndrome (GS) is a rare primary immunodeficiency in adults consisting of hypogammaglobulinemia and thymoma that affects both cellular and humoral immunity. It usually appears in patients between the 4th and 6th decade of life and affects both genders equally. Ophthalmological clinical presentation is highly variable; associations with herpetic keratitis, toxoplasmosis, and cytomegalovirus retinitis (CMVR) have been described. GS associated with CMVR is uncommon. Ophthalmologists may be the first to diagnose systemic disease and change the outcome...

No abstract text is available yet for this article.

The aim of the present study was to determine humoral and T-cell responses after four doses of mRNA-1273 vaccine in solid organ transplant (SOT) recipients, and to study predictors of immunogenicity, including the role of previous SARS-CoV-2 infection in immunity. Secondarily, safety was also assessed. Liver, heart, and kidney transplant recipients eligible for SARS-CoV-2 vaccination from three different institutions in Barcelona, Spain were included. IgM/IgG antibodies and T cell ELISpot against the S protein four weeks after receiving four consecutive booster doses of the vaccine were analyzed...