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Eur J Case Rep Intern Med. 2025 Jun 5;12(7):005480. doi: 10.12890/2025_005480. eCollection 2025.

ABSTRACT

Thymus is a primary lymphoid organ whose main function is the education of the T lymphocytes. Thymoma is uncommon neoplasia derived from epithelial cells of the thymus. Patients with thymoma frequently present with autoimmune disorders, mostly myasthenia gravis. Good’s syndrome (GS) is an acquired adult-onset combined immunodeficiency typically characterised by the triad of thymoma, hypogammaglobulinaemia and increased susceptibility to recurrent infections. Immunoglobulin replacement is the main therapeutic strategy. Our knowledge of thymoma-associated immunodeficiency is predominantly derived from case reports or small series. We report the case of a patient with recurrent sigmoid diverticulitis that appeared after a thymectomy, who was subsequently found to have severe hypogammaglobulinaemia.

LEARNING POINTS: Good’s syndrome is a rare, acquired, adult-onset immunodeficiency.Good’s syndrome remains an enigmatic disease.Immunoglobulin replacement is the main therapeutic strategy.

PMID:40636243 | PMC:PMC12236679 | DOI:10.12890/2025_005480

Eur J Cancer. 2025 Jul 5;226:115598. doi: 10.1016/j.ejca.2025.115598. Online ahead of print.

ABSTRACT

BACKGROUND: Inborn errors of immunity (IEI) and inherited bone marrow failure syndromes (IBMFS) are associated with an increased lifetime cancer risk. However, the role of most IEI/IBMFS in childhood cancer predisposition remains largely unexplored. This study investigated the potential contribution of germline variants in IEI/IBMFS-associated genes to pediatric hematological malignancy development.

METHODS: We analyzed 151 children with leukemia or lymphoma for germline (likely) pathogenic variants in 541 IEI/IBMFS-associated genes. None had features indicative of IEI/IBMFS prior to their cancer diagnosis.

RESULTS: Six patients (4 %) had monoallelic (likely) pathogenic variants in autosomal dominant genes (TNFRSF13B, MPL, AIRE, NLRP12). Thus far, these genes have no proven association with childhood cancer predisposition. The carrier frequency of monoallelic (likely) pathogenic variants in recessive genes was 33 %, considered to align with general population data. Twelve patients (8 %) carried variants in genes involved in DNA repair or chromosomal stability, half of which had been identified in previous work by our group or were known before the cancer diagnosis.

CONCLUSION: This study assessed for the first time in an unbiased and comprehensive manner the role of IEI/IBMFS in childhood hematological malignancy predisposition. Although the overall yield of this exploratory study was limited, our findings support the importance of research on childhood cancer predisposition at the intersection of hematological malignancies and IEI/IBMFS. We identified several variants in both dominant and recessive genes of which it would be interesting to investigate their causality. However, for now, sequencing of IEI/IBMFS-associated genes should be restricted to research context or in case of clinical suspicion.

PMID:40633199 | DOI:10.1016/j.ejca.2025.115598

Clin Case Rep. 2025 Jul 7;13(7):e70605. doi: 10.1002/ccr3.70605. eCollection 2025 Jul.

ABSTRACT

Prurigo nodularis is a chronic pruritic condition that leads to a vicious itch-scratch cycle, which can significantly impair quality of life. Low-dose methotrexate is an effective option for patients with chronic nodular prurigo not responding to topical therapy, offering a favorable safety profile and improving their quality of life.

PMID:40630750 | PMC:PMC12235048 | DOI:10.1002/ccr3.70605

Am J Case Rep. 2025 Jul 9;26:e947678. doi: 10.12659/AJCR.947678.

ABSTRACT

BACKGROUND Selective immunoglobulin A deficiency (SIgAD) is the most common primary immunodeficiency. However, most people with SIgAD are asymptomatic, and it is typically diagnosed during screening for blood donations or unexpected transfusion reactions. Screening programs for IgA deficiency have not yet been established, and the exact etiology of IgA deficiency remains unclear. CASE REPORT We report a case of SIgAD in a man who was diagnosed after a febrile non-hemolytic transfusion reaction (FNHTR) during erythrocyte transfusion for severe anemia. A 70-year-old man with a history of surgery for gastric carcinoid and sigmoid colon cancer presented to our hospital with persistent fatigue and general malaise for 2 months. A blood test revealed severe anemia with hyperbilirubinemia at the first visit to our hospital, and an erythrocyte transfusion was performed. A fever of 39.4°C with shivering was observed 30 min after the start of the transfusion. On day 20 after discharge, the serum IgA level was <3 µg/dL, indicating a high probability of IgA deficiency. He also tested positive for serum anti-IgA antibodies, leading to a diagnosis of SIgAD. CONCLUSIONS The cause of transfusion reaction should be immediately investigated, and the physician needs to learn about the epidemiology of transfusion reaction. Once the cause of transfusion reaction is identified, appropriate instruction should be provided for the patient to avoid transfusion reactions, and patients with SIgAD may benefit from wearing a medical alert bracelet.

PMID:40629683 | DOI:10.12659/AJCR.947678

JCI Insight. 2025 Jul 8:e174235. doi: 10.1172/jci.insight.174235. Online ahead of print.

ABSTRACT

Hematopoietic Protein-1 (Hem1) is a component of the WASP-family verprolin-homologous protein (WAVE) actin regulatory complex, which is activated downstream of multiple immune receptors. Mutations in the NCKAP1L gene encoding HEM1 have recently been found to result in severe Primary Immunodeficiency Disease (PID), characterized by recurrent respiratory infections, hyperinflammation, autoimmunity, and high mortality. However, how loss of Hem1 results in PID is unclear. To define the importance of Hem1 specifically in T cells, we generated constitutive and T cell specific Hem1 null mice. Hem1 deficient T cells exhibited an increased shift from naïve to memory T cells, and increased ratio of immunosuppressive regulatory to effector T cells. Loss of Hem1 resulted in hallmarks of T cell exhaustion including T cell lymphopenia, decreased activation and proliferation, increased expression of PD-1 and Tim3, and increased IL-10 production. In vitro TCR stimulation of CD4 T cells resulted in increased production of Th1 (IFN), Th2 (IL-5, IL-13), Th17 (IL-17, IL-22), and Treg (IL-10) cytokines. This correlated with reduced F-actin, increased expression of CD107a, and increased granzyme release indicative of increased granule membrane fusion and exocytosis. These results suggest that Hem-1 is critical for maintaining T cell activation, homeostasis and regulated cytokine production following antigen encounter.

PMID:40627451 | DOI:10.1172/jci.insight.174235

Pediatr Discov. 2024 May 27;2(3):e67. doi: 10.1002/pdi3.67. eCollection 2024 Sep.

ABSTRACT

Primary immunodeficiency diseases (PIDs) present a heterogeneous group of diseases with aberrant immune response caused by monogenic mutations. Due to the immune dysfunction and dysregulation, PIDs have a wide clinical spectrum such as infections, autoimmunity, autoinflammation, allergy, and malignancies. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized with multiple autoantibodies and multiple organ damage, which could be the predominant phenotype in patients with PIDs. In recent years, the increasing identification of monogenic causes of SLE and PIDs discloses the partially shared genetic background and common pathogenic process. The study of PIDs with SLE-like phenotype paves the way for the exploration of lupus pathogenesis and new perspectives in targeted therapies concurrently.

PMID:40625455 | PMC:PMC12118181 | DOI:10.1002/pdi3.67

BMC Ophthalmol. 2025 Jul 7;25(1):395. doi: 10.1186/s12886-025-04230-5.

ABSTRACT

BACKGROUND: Adenosine deaminase-2 (ADA2) deficiency is a rare autosomal recessive autoinflammatory syndrome, typically presenting in young patients with a broad spectrum of phenotypes. These phenotypes usually include primary immune deficiencies, livedo reticularis, and hematological abnormalities. Visual loss associated with ADA2 deficiency is uncommon and, when it does occur, is often linked to major vascular involvement, such as occlusion of the ophthalmic arteries. Paracentral acute middle maculopathy (PAMM) is an optical coherence tomography (OCT) finding characterized by ischemia at the inner retinal capillary complex rather than the major retinal vessels. It has been previous associated with a variety of systemic diseases, retinal vascular diseases, and drugs side-effects, but never with ADA2 deficiency until this moment.

CASE PRESENTATION: A 31-year-old woman with a presumptive diagnosis of common variable immunodeficiency and livedo reticularis presented with sudden onset severe visual loss in the left eye due to PAMM followed a few weeks later by a lacunar stroke. An extensive laboratory investigation including genetic testing led to the diagnosis of ADA2 deficiency, a rare recessively inherited autoinflammatory syndrome. Treatment regimen was switched to anti-TNF-α inhibitors, leading to disease remission with no further vascular events over a two-year follow-up period.

CONCLUSION: This case serves to emphasize the importance of considering ADA2 deficiency in patients with PAMM, particularly when it occurs in young patients with a history of strokes and/or immunological abnormalities.

PMID:40624633 | DOI:10.1186/s12886-025-04230-5

Zhonghua Xue Ye Xue Za Zhi. 2025 May 14;46(5):402-409. doi: 10.3760/cma.j.cn121090-20250112-00024.

ABSTRACT

The number of immunocompromised individuals in China is rapidly increasing, and the incidence of cytomegalovirus (CMV) infection in this population is significantly higher than in the general population, severely affecting their quality of life and prognosis. Currently, a standardized diagnostic and treatment system for refractory/resistant CMV infections in immunocompromised populations is lacking. Based on domestic and international data on the epidemiology, evidence-based medicine, and clinical research regarding refractory/resistant CMV infections, this consensus formulates recommendations for the diagnosis, treatment, and management of these infections.

PMID:40623898 | DOI:10.3760/cma.j.cn121090-20250112-00024

BMJ Case Rep. 2025 Jul 7;18(7):e265178. doi: 10.1136/bcr-2025-265178.

ABSTRACT

A preadolescent male, born to 3rd-degree consanguineous parents, presented with persistent fever, cough and dyspnoea. He had non-resolving suppurative otitis media and two episodes of pneumonia in the past 2 years. During admission, clinical and radiological evaluations revealed bilateral lung consolidation with synpneumonic effusion. Examination also revealed the absence of bilateral tonsils. Blood and pleural fluid cultures were sterile. The child developed a drug reaction with eosinophilia and systemic symptoms (DRESS) associated with haemophagocytic-lymphohistiocytic syndrome (HLH) during the hospital stay. Given his history of recurrent infections and absent tonsils, primary immunodeficiency disorder was suspected. Immunological work-up showed reduced levels of IgG and IgM in serum. Exome sequencing identified a mutation in the SH2D1A gene confirming a diagnosis of X-linked lymphoproliferative syndrome (Duncan syndrome). The child was started on regular intravenous immunoglobulin therapy, along with bacterial and fungal prophylaxis. His parents were counselled regarding the prognosis and necessity of haematopoietic stem cell transplantation as the definitive treatment.

PMID:40623777 | DOI:10.1136/bcr-2025-265178

J Allergy Clin Immunol Pract. 2025 Jul 7:S2213-2198(25)00536-7. doi: 10.1016/j.jaip.2025.05.059. Online ahead of print.

ABSTRACT

Immunoglobulin replacement therapy is a fundamental treatment option to protect against infection for most patients with a primary deficiency in antibody production. Facilitated subcutaneous immunoglobulin (fSCIG) 10% is an immunoglobulin replacement therapy that uses recombinant human hyaluronidase to enhance immunoglobulin dispersion and absorption. This review provides an overview of data published to date relating to the safety and tolerability of fSCIG 10% for the treatment of primary immunodeficiency diseases in pediatric patients. Eight studies (199 pediatric patients) were included for discussion. fSCIG 10% displays a low rate of treatment-related systemic adverse events, and the risk of treatment-related local adverse events diminishes with increased treatment exposure. The reduced number of needle sticks required for fSCIG 10% administration than for conventional subcutaneous immunoglobulin may offer advantages for patients with immune disorders that have compromised their skin integrity, and for those who experience needle phobia and treatment-associated anxiety. Studies evaluating prospective, patient-centric data collected on the experience of such patients may be a valuable addition to the evidence base. Discussion of fSCIG 10% as a potential treatment option between families and health care professionals will enhance individualized treatment plans and shared decision making, which are important considerations for patients with primary immunodeficiency diseases.

PMID:40622324 | DOI:10.1016/j.jaip.2025.05.059