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Clin Case Rep. 2024 Dec 17;12(12):e70007. doi: 10.1002/ccr3.70007. eCollection 2024 Dec.

ABSTRACT

LIG4 syndrome is an exceptionally rare primary immune deficiency. It is an autosomal recessive genetic disease, falling within the spectrum of genetic disorders characterized by impaired DNA damage response mechanisms. Common clinical characteristics encompass microcephaly, growth retardation, developmental delays, facial deformities, variable immune deficiencies, pancytopenia, heightened susceptibility to malignant tumors, and significant clinical and cellular radiosensitivity. Hematopoietic stem cell transplantation (HSCT) is a curative treatment for LIG4 syndrome and may mitigate the long-term risk of developing lymphoid malignancies by improving tumor surveillance.

PMID:39698004 | PMC:PMC11652113 | DOI:10.1002/ccr3.70007

BMC Infect Dis. 2024 Dec 18;24(1):1399. doi: 10.1186/s12879-024-10281-8.

ABSTRACT

X-linked lymphoproliferative disease (XLP) is a rare primary immunodeficiency with susceptibility and vulnerability to Epstein-Barr virus (EBV) infection. Most patients were diagnosed in early childhood and do not survive into adulthood. Here we reported an adult-onset XLP patient presenting with fever, dyspnea, and pulmonary nodules, mimicking respiratory infection at disease onset. Diagnosis was made based on whole-exon sequencing and pedigree analysis. Chest CT showed bilateral nodular lesions partially responsive to steroid therapy. The symptoms were managed with high-dose steroid, together with broad-spectrum anti-infective treatment for mixed secondary opportunistic infections. Pathology studies revealed non-Langerhans histiocytosis and T cell infiltration in lungs. Our case highlights the importance of genetic sequencing in managing young patients with unexplained infection and potential immuno-deficiency. We also added to the understanding of XLP by carrying detailed investigation into the pulmonary lesions.

PMID:39696021 | DOI:10.1186/s12879-024-10281-8

J Clin Immunol. 2024 Dec 17;45(1):57. doi: 10.1007/s10875-024-01838-y.

ABSTRACT

PURPOSE: Significant improvements in the prognosis for young patients with Primary Immunodeficiency Diseases (PID) and Autoinflammatory Disorders (AID), which together make up the majority of Inborn Errors of Immunity (IEI), have resulted in the need for optimisation of transition and transfer of care to adult services. Effective transition is crucial to improve health outcomes and treatment compliance among patients. Evaluations of existing transition programmes in European health centres identified the absence of disease-specific transition guidelines for PID and AID, as a challenge to the transition process. This research aimed to establish expert consensus statements for the transition of young patients with PID and AID to adult services.

METHODS: This project used the Delphi method to establish mutual agreement for the proposed recommendations. A draft set of statements was developed following a literature review of existing transition programmes. Then the ERN RITA Transition Working Group convened to review the drafted recommendations and develop them into a survey. This survey was circulated among healthcare professionals to determine consensus using a five-point Likert scale, with the level of agreement set to 80% or greater. Statements that did not reach consensus were revised by the Working Group and recirculated among respondents.

RESULTS: The initial survey received 93 responses from 68 centres across 23 countries, while the following survey outlining revised recommendations received 66 responses. The respondents agreed upon recommendations detailing the structure and administration of transition programmes, collaborative working with social systems, and contraindications to transfer of care.

CONCLUSION: This paper sets out a comprehensive set of recommendations to optimise transitional care for PID and AID.

PMID:39690292 | DOI:10.1007/s10875-024-01838-y

J Clin Immunol. 2024 Dec 17;45(1):56. doi: 10.1007/s10875-024-01848-w.

ABSTRACT

PURPOSE: Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder characterized by distinctive features including microthrombocytopenia, eczema and recurrent infections. In the present study we report clinical, immunological and molecular spectrum of 41 WAS patients diagnosed over last five years.

METHODS: Clinical and family history was collected from case records. Comprehensive immunological assessments including lymphocyte subset analysis, and flow cytometry based evaluation of WAS protein (WASP) expressions were performed in patients along with evaluation of carrier status in mothers. Genetic analysis was carried out with either Sanger sequencing or targeted exome sequencing.

RESULTS: The patients included in this study presented at a median age of 9.5 months, with two adult cases. Clinical manifestations encompassed thrombocytopenia, eczema, bleeding, diarrhea, respiratory tract infections, CMV infection, and malignancy. Immunological phenotype revealed T cell lymphopenia, B cell lymphopenia, and elevated IgE levels. Flow cytometry analysis of WASP was performed in 36 cases out of which 68.42% demonstrated complete absent expression while others showed reduced expression. Genetic analysis highlighted that the majority of mutations affect the WH1 domain of WASP while both adult patients showed intronic mutations. Molecular Dynamics analysis conducted for the novel variants P398R and G33R showed an average RMSD (Å) higher than that of the wild type, indicating greater structural perturbations in WASP.

CONCLUSION: In the present study we have documented 56.09% novel WAS mutations in Indian cohort. Notably, the application of flow cytometry has emerged as a valuable and efficient diagnostic tool for identifying these WAS patients.

PMID:39688652 | DOI:10.1007/s10875-024-01848-w

Dermatol Reports. 2024 Jul 3;16(4):9939. doi: 10.4081/dr.2024.9939. eCollection 2024 Nov 21.

ABSTRACT

Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency condition caused by a genetic abnormality that increases the risk of recurrent and persistent skin, nail, and mucous membrane infections with Candida species, typically Candida albicans. Signal transducer and activator of transcription 1 (STAT1) gene mutation is a genetic trigger that causes CMC, which increases the risk of infections, multisystem disorders, and cancer susceptibility. We describe the first case of a Saudi female patient with clinical features of CMC with an underlying (STAT1) gene mutation.

PMID:39687689 | PMC:PMC11647450 | DOI:10.4081/dr.2024.9939

World J Clin Cases. 2024 Dec 16;12(35):6840-6847. doi: 10.12998/wjcc.v12.i35.6840.

ABSTRACT

BACKGROUND: Cat scratch disease (CSD) is the most common human infection caused by Bartonella henselae (B. henselae). The main manifestation is self-limited lymphadenopathy that primarily affects adolescents, and typically resolves without treatment within 2-4 months. However, individuals with compromised immune systems or immunodeficiency require specific antibacterial therapy following diagnosis. Due to its low incidence, nonspecific clinical manifestations, and diagnostic limitations, this condition often poses challenges for clinicians in terms of missed diagnoses and misdiagnoses.

CASE SUMMARY: The child was ultimately diagnosed with CSD. The primary manifestations included nocturnal fever, enlargement of lymph nodes in the neck, axilla and groin, and suspected brucellosis; however, both brucellosis tests conducted during the course of the illness yielded negative results. Bone marrow cytology indicated stimulated proliferation. Lymph node biopsy indicated hyperplasia of lymphoid tissue in the cervical lymph nodes (right), with combined immunohistochemical findings indicating reactive hyperplasia. Immunohistochemical analysis revealed CD20 B (+), CD3 T (+), BCL-6 (+), and BCL-2 (-). CD21 FDC networks were present and Ki67 expression in the germinal center was ~80%. Blood next-generation sequencing indicated B. henselae sequence number was 3. Serological test results demonstrated positive antibody response to B. henselae IgG (+), B. henselae IgM (+), Bartonella quintana (B. quintana) IgG (-) and B. quintana IgM (-), and the final diagnosis was CSD.

CONCLUSION: In patients presenting with fever at night and swollen lymph nodes of unknown origin, CSD should be considered.

PMID:39687640 | PMC:PMC11525915 | DOI:10.12998/wjcc.v12.i35.6840

Nutrients. 2024 Dec 9;16(23):4242. doi: 10.3390/nu16234242.

ABSTRACT

Background: Small vulnerable newborns (SVNs), including those born preterm, small for gestational age, or with low birth weight, are at higher risk of neonatal mortality and long-term health complications. Early exposure to maternal vaginal microbiota and breastfeeding plays a critical role in the development of the neonatal microbiota and immune system, especially in low-resource settings like Burkina Faso, where neonatal mortality rates remain high. Objectives: The DenBalo study aims to investigate the role of maternal and neonatal factors, such as vaginal and gut microbiota, immune development, and early nutrition, in shaping health outcomes in SVNs and healthy infants. Methods: This prospective cohort observational study will recruit 141 mother-infant pairs (70 SVNs and 71 healthy controls) from four health centers in Bobo-Dioulasso, Burkina Faso. The mother-infant pairs will be followed for six months with anthropometric measurements and biospecimen collections, including blood, breast milk, saliva, stool, vaginal swabs, and placental biopsies. Multi-omics approaches, encompassing metagenomics, metabolomics, proteomics, and immune profiling, will be used to assess vaginal and gut microbiota composition and functionality, immune cell maturation, and cytokine levels at critical developmental stages. Conclusions: This study will generate comprehensive data on how microbiota, metabolomic, and proteomic profiles, along with immune system development, differ between SVNs and healthy infants. These findings will guide targeted interventions to improve neonatal health outcomes and reduce mortality, particularly in vulnerable populations.

PMID:39683635 | DOI:10.3390/nu16234242

Immunother Adv. 2024 Nov 7;4(1):ltae009. doi: 10.1093/immadv/ltae009. eCollection 2024.

ABSTRACT

The phosphoinositide-3-kinase (PI3K) pathway function is crucial to the normal development, differentiation, and function of immune cells including B, T, and NK cells. Following the description of two cohorts of patients with an inboirn error of immunity (also known as primary immunodeficiency) with gain-of-function variants in the PIK3CD gene a decade ago, the disease entity activated PI3K delta syndrome (APDS) was named. Since then, many more patients with PIK3CD variants have been described, and loss-of-function variants in PIK3R1 and PTEN have also been linked to APDS. Importantly, the availability of small molecules that inhibit the PI3K pathway has enabled targeted treatment of APDS patients. In this review, we define (i) the PI3K pathway and its role in inborn errors of immunity; (ii) the clinical and immunological presentation of APDS1 (PIK3CD GOF), APDS2 (PIK3R1 LOF), and related disorders; (iii) Diagnostic approaches to identify and functionally validate the genetic causes of disease; (iv) therapeutic interventions to target PI3K hyperactivation; and finally (v) current challenges and future perspectives that require attention for the optimal treatment of patients with APDS and APDS-L diseases.

PMID:39679264 | PMC:PMC11638974 | DOI:10.1093/immadv/ltae009

Ann Allergy Asthma Immunol. 2024 Dec 12:S1081-1206(24)01726-5. doi: 10.1016/j.anai.2024.12.003. Online ahead of print.

ABSTRACT

Hypogammaglobulinemia is defined as a reduced immunoglobulin level, which can be either primary due to inborn errors of immunity or acquired in the setting of poor antibody production or increased antibody loss. Secondary hypogammaglobulinemia (SHG) should be considered in patients with a history of immunosuppressive therapy, transplant, protein loss syndromes, certain autoimmune conditions, and malignancies, as it can be associated with increased infectious risk. Appropriate history and lab-based screening in these populations can identify SHG allowing treatment and close monitoring as appropriate. Ideally, treatment focuses on control of underlying condition or removal of iatrogenic causes of SHG. However, in many cases, treatment of the underlying condition does not reverse SHG, or immunosuppressive therapy cannot be discontinued without significant risk to the patient. For these patients, strategies for risk mitigation against infectious complications include vaccination, antibiotic prophylaxis and immunoglobulin replacement therapy. This report aims to summarize the existing and emerging data in evaluation and management of SHG and highlight areas which require further investigation.

PMID:39674275 | DOI:10.1016/j.anai.2024.12.003

Iran Biomed J. 2024 Dec 1;28(7):83.

ABSTRACT

INTRODUCTION: One in every 50,000 to 100,000 live births is estimated to be affected by severe combined immunodeficiency (SCID). SCID is a primary immunodeficiency disorder characterized by severe cellular and humoral immunity defects, leading to increased susceptibility to infections. Typically, SCID presents in early infancy with recurrent and opportunistic infections, failure to thrive, and a high mortality rate if left untreated. Treatment options for SCID include allogeneic hematopoietic stem cell transplantation (HCT) or gene therapy to correct the function of immune cells. The purpose of this study was to systematically review the therapeutic effects of stem cell transplantation in patients with SCID.

METHODS AND MATERIALS: The study was conducted based on the PICO criteria and aligned with the research objective, adhering to the PRISMA checklist. This systematic review included a comprehensive search from 2019 to March 2024 in the PubMed, SCOPUS, and Web of Science databases, the Google Scholar search engine, and the Persian databases SID and Magiran. The MESH keywords used for the search were “SCID”, “Stem cell”, “Transplantation”, and “Therapy”. Subsequently, two independent researchers screened the retrieved articles based on inclusion criteria.

RESULTS: A total of 274 articles were identified during the initial search. After removing duplicates and screening titles and abstracts, the number of articles was reduced to 16. Finally, after considering the inclusion and exclusion criteria and reviewing the full text, six articles were included in this study. Most of the studies showed that stem cell transplantation is a treatment with minimal short- and long-term toxicity in patients with SCID and leads to improved immune system reconstitution, resistance to opportunistic infections, long-term survival in more than 70% of cases, and improved quality of life in patients with SCID.

CONCLUSION AND DISCUSSION: Stem cell transplantation can be an effective treatment for patients with SCID and can reduce disease complications, the burden of care, and associated healthcare costs. However, more research is needed to confirm this approach and establish its clinical application due to the limitations of the studies conducted in this field.

PMID:39673158