Manish Butte

Pan Afr Med J. 2024 Oct 11;49:33. doi: 10.11604/pamj.2024.49.33.42418. eCollection 2024.

ABSTRACT

Hyper immunoglobulin M (IgM) syndromes are a collection of uncommon primary combined immunodeficiency disorders. They are characterized by recurrent bacterial infections due to low levels of IgG, IgA, and IgE, while IgM levels remain normal or high. These conditions stem from a mutation in the CD40 ligand gene or disruptions in the CD40-signaling pathway. Those affected face increased susceptibility to frequent bacterial infections, an elevated likelihood of autoimmune issues, and early-onset malignancies. These syndromes are rare and account for a small fraction of immunodeficiency cases. We describe a case of an African infant, who had a prolonged pediatric intensive care unit admission due to recurrent and severe infections which took a prolonged course of medication to be treated. After a diagnostic workup, a diagnosis of X-linked hyper IgM syndrome was established, and currently, our child is on monthly replacement of IV immunoglobulin and daily prophylactic cotrimoxazole tablets. Early diagnosis of primary immunodeficiency disorders reduces the incidence of infections and the severity of complications. This case demonstrates the consequences of delayed diagnosis and resulting in a prolonged hospital stay.

PMID:39886113 | PMC:PMC11781210 | DOI:10.11604/pamj.2024.49.33.42418

Leuk Lymphoma. 2025 Jan 28:1-15. doi: 10.1080/10428194.2025.2456970. Online ahead of print.

ABSTRACT

Over the past two decades, there has been a continuous improvement in outcome for patients with indolent lymphoma (iNHL) resulting in a gradual accumulation of survivors. While life expectancy in the current era approaches that of the lymphoma-free population, patients continue to experience lifelong complications of the disease and its treatment affecting general health, emotional, psychological and social wellbeing, relationships, employment, finances, and fitness. Contemporary care models while suited to the management of lymphoma are often lacking when it comes to identification and management of these additional needs. Given improvements in physical survival achieved over the past decades, it is timely for us to focus on other issues affecting patient wellbeing including immunodeficiency and infection, second cancers, cardiovascular disease, bone health, psychological wellbeing, and sexual health. Many of these aspects are in the domain of the primary care physician; however, there is limited guidance on how these issues should be addressed. It is now time for us to engage our patients, their caregivers, and other healthcare providers in care aspects beyond the lymphoma diagnosis, so they can anticipate a rich and full life, free from both direct and indirect consequences of the lymphoma diagnosis.

PMID:39876569 | DOI:10.1080/10428194.2025.2456970

Wiad Lek. 2024;77(12):2475-2480. doi: 10.36740/WLek/197084.

ABSTRACT

OBJECTIVE: Aim: To investigate the effect of succinic acid on the humoral component of the immune system in rats.

PATIENTS AND METHODS: Materials and Methods: The study was conducted on two groups of mature non-linear white rats (males) of similar weight (200-270 g, aged 6-8 months), with 5 animals in each group. The control group was fed a standard diet with free access to water throughout the experiment. Rats in the experimental group were subcutaneously injected with a 0,1% solution of succinic acid in a liposomal emulsion at a dose of 20 cm³ for five days. The state of the humoral component of the immune system was assessed by measuring serum immunoglobulins A, M, and G using solid-phase enzyme-linked immunosorbent assay. Circulating immune complexes were determined in a 40% solution of polyethylene glycol.

RESULTS: Results: Under the influence of succinic acid in liposomal emulsion the content of class A immunoglobulins increased by 44,0% (p<0.01) compared to rats in the control group. The activation of class A immunoglobulin synthesis points to the provision of local immunity of the mucous membranes in the rat’s body. The content of class M immunoglobulins increased by 61,0% (p<0.001) compared to the control group rats. This high activity of class M immunoglobulins indicates their rapid activation in the body of rats in response to primary contact with succinic acid in liposomal emulsion. The content of class G immunoglobulins increased by 36,0% (p<0.05) compared to the control group rats. No clinical deviations from physiological norms were observed in the rats after the use of succinic acid in liposomal emulsion. After the use of succinic acid in liposomal emulsion in the experimental group of rats, the concentration of CICs increased by 15,0% (p<0.05) compared to the control group rats. In our case, the increase in CIC levels is not correlated with clinical manifestations but is a consequence of increased levels of class M and G immunoglobulins.

CONCLUSION: Conclusions: The succinic acid in liposomal emulsion activates the production of class A, M, G immunoglobulins, circulating immune complexes, it prevents the development of secondary immunodeficiency and has a positive impact on the humoral branch of the immune system in rats.

PMID:39874332 | DOI:10.36740/WLek/197084

Front Immunol. 2025 Jan 13;15:1517543. doi: 10.3389/fimmu.2024.1517543. eCollection 2024.

ABSTRACT

Activated PI3K delta syndrome (APDS) is a primary immunodeficiency that is caused by mutations in the PI3K signalling pathway resulting in either gain-of-function or loss-of-function phenotypes of APDS 1 and 2. Malignancy is one of the most serious complications associated with APDS patients, with the most commonly occurring of these being lymphoma, and is the most common cause of death in APDS patients. Management of APDS is complex and variable due to the heterogeneous nature of the disease and ranges from antimicrobial and immunosuppressant agents to haematopoetic stem cell transplantation. More recently, an increasing level of interest has been shown in the use of more targeted agents such as PI3Kδ-specific inhibitors. Here, we provide expert perspective on the suspected causality of a case of lymphoma observed in a 20-year-old female patient who was included in a clinical trial of leniolisib, a PI3K inhibitor.

PMID:39872539 | PMC:PMC11770023 | DOI:10.3389/fimmu.2024.1517543

Tremor Other Hyperkinet Mov (N Y). 2025 Jan 20;15:4. doi: 10.5334/tohm.992. eCollection 2025.

ABSTRACT

BACKGROUND: Ataxia-telangiectasia (Louis-Bar syndrome) is a rare genetic disorder characterized by progressive ataxia, ocular telangiectasias, immunodeficiency and increased cancer risk due to impaired DNA repair.

PHENOMENOLOGY SHOWN: Thorough clinical and subsequently radiological examination in a 19-year-old woman with a history of previously undiagnosed, progressive gait ataxia since early childhood, diffuse large B-cell lymphoma and severe combined immunodeficiency revealed the eponymous features of the disease, ocular telangiectasias and cerebellar atrophy, enabling targeted genetic testing.

EDUCATIONAL VALUE: Ocular telangiectasias represent an important clue for a diagnosis of ataxia-telangiectasia in young patients with progressive ataxia, implicating awareness of increased malignancy risk and treatment of immunodeficiency.

HIGHLIGHTS: Ataxia-telangiectasia is a rare genetic disorder characterized by its eponymous features, progressive cerebellar ataxia and ocular telangiectasias. These signs can help in establishing an early diagnosis, hence preventing, or addressing secondary complications of the disease caused by impaired DNA repair, such as malignancies, immunodeficiency, and increased radiation sensitivity.

PMID:39867503 | PMC:PMC11758811 | DOI:10.5334/tohm.992

Cell Mol Biol Lett. 2025 Jan 26;30(1):12. doi: 10.1186/s11658-025-00691-0.

ABSTRACT

Vacuolization of hematopoietic precursors cells is a common future of several otherwise non-related clinical settings such as VEXAS, Chediak-Higashi syndrome and Danon disease. Although these disorders have a priori nothing to do with one other from a clinical point of view, all share abnormal vacuolization in different cell types including cells of the erythroid/myeloid lineage that is likely the consequence of moderate to drastic dysfunctions in the ubiquitin proteasome system and/or the endo-lysosomal pathway. Indeed, the genes affected in these three diseases UBA1, LYST or LAMP2 are known to be direct or indirect regulators of lysosome trafficking and function and/or of different modes of autophagy. Furthermore, all three genes are highly expressed in the more mature myeloid cells pointing out their likely important function in these cells. LAMP2 deficiency for instance is known to be associated with alterations of lysosome architecture and function. It is thus well established that different cell types from Danon disease patients that harbor invalidating mutations in LAMP2 exhibit giant lysosomes containing undigested materials characteristic of defects in the fusion of lysosomes with autophagosomes, a feature also found in VEXAS and CHS. Other similarities regarding these three diseases include granulocyte and monocyte dysfunctions and a recurrent inflammatory climate. In the present review we discuss the possibility that some common clinical manifestations of these diseases, notably the hematopoietic ones are consecutive to a dysfunction of the endo-lysosomal pathway in myeloid/erythroid progenitors and in mature myeloid cells including neutrophiles, monocytes and macrophages. Finally, we propose reacidification as a way of reinducing lysosome functionalities and autophagy as a potential approach for a better management of these diseases.

PMID:39865233 | DOI:10.1186/s11658-025-00691-0

BMC Infect Dis. 2025 Jan 25;25(1):120. doi: 10.1186/s12879-025-10488-3.

ABSTRACT

BACKGROUND: Mycobacterium avium complex (MAC) is a common pathogen causing non-tuberculous mycobacterial infections, primarily affecting the lungs. Disseminated MAC disease occurs mainly in immunocompromised individuals, such as those with acquired immunodeficiency syndrome, hematological malignancies, or those positive for anti-interferon-γ antibodies. However, its occurrence in solid organ transplant recipients is uncommon. Herein, we report a rare case of disseminated MAC disease following liver transplantation, which led to an obstructive mass in the intestinal tract that required differentiation from a malignant tumor.

CASE PRESENTATION: A 76-year-old woman, who had undergone living-donor liver transplantation 15 years earlier for primary biliary cirrhosis, presented with persistent fever and vomiting three months before admission. She had a history of pulmonary MAC diagnosed five years earlier but remained untreated due to stable lung lesions. Abdominal computed tomography (CT) during her current illness revealed new thickening at the jejuno-jejunal anastomosis site and enlarged mesenteric lymph nodes. Positron emission tomography-CT indicated increased uptake at these sites, suggesting a possible malignancy. Endoscopy revealed an elevated lesion with circumferential ulcers, leading to a suspicion of primary malignant lymphoma. However, biopsies showed CD68-positive histiocyte-like cells with numerous acid-fast bacilli, confirming disseminated MAC infection. Despite ongoing antimicrobial therapy, the patient’s intestinal lesions persisted, and she required prolonged hospitalization and interventions for bile drainage and enteral nutrition.

CONCLUSION: This case underscores the importance of considering disseminated MAC as a potential complication in solid organ transplant recipients, even when a long period has passed since transplantation. Disseminated MAC can mimic malignancy, presenting with significant lesions causing intestinal obstruction. Awareness and thorough differential diagnosis are essential for timely and accurate management in such complex cases. The patient’s outcome emphasizes the need for vigilance in managing long-term immunosuppressed patients, particularly when they present with atypical infections.

PMID:39863833 | DOI:10.1186/s12879-025-10488-3

Zhonghua Bing Li Xue Za Zhi. 2025 Feb 8;54(2):203-209. doi: 10.3760/cma.j.cn112151-20241209-00838.

ABSTRACT

极早发炎症性肠病是6岁之前儿童发生的具有炎症性肠病样症状的一组疾病，包括真正的炎症性肠病和单基因炎症性肠病（mIBD），后者涉及多种与原发免疫缺陷相关基因。极早发炎症性肠病，包括mIBD，病理组织学表现多样，临床表现及临床治疗反应均存在不同。本文总结了近年认识的常见mIBD和极早发炎症性肠病的病理诊断进展。.

PMID:39863544 | DOI:10.3760/cma.j.cn112151-20241209-00838

J Clin Med. 2025 Jan 14;14(2):497. doi: 10.3390/jcm14020497.

ABSTRACT

Background/Objectives: Gastrointestinal diseases are a major cause of morbidity in common variable immunodeficiency disorder (CVID), clinically often mimicking other conditions including celiac disease and inflammatory bowel disease (IBD). Hence, diagnosis of CVID remains challenging. This study aims to raise awareness and highlight histopathological clues for CVID in intestinal biopsies, emphasizing diagnostic pitfalls for the pathologist/gastroenterologist. Methods: We reviewed 63 (18 duodenal, 23 ileal, 22 colonic) biopsies and case histories from seven CVID patients, obtained over a 31-year period, with attention to active inflammation, intraepithelial lymphocytes, plasma cells, lymphoid hyperplasia, crypt/villous architecture, subepithelial collagen, apoptosis, granulomas, and infections. Clinical information of 41 pathology requests was reviewed. Results: Gastrointestinal symptoms were variable. Histological features included IBD-like (3/7), celiac disease-like (2/7), graft-versus-host disease (GVHD)-like (2/7), lymphocytic sprue/colitis-like (3/7), collagenous colitis-like (2/7), and acute colitis-like (4/7) patterns, often overlapping (2/7) and/or changing over time (3/7). Lymphoid hyperplasia was seen in 3/7 patients; 1/7 had giardiasis; and 5/7 had few plasma cells, usually only in part of the gut (3/5). Clinical information of 12/41 (29%) pathology requests mentioned known/suspected CVID, despite being known in 33/41 (80%). Conclusions: Clinical/histological features of CVID in the gut are diverse, often mimicking IBD, microscopic colitis, celiac disease and/or GVHD, hence the importance of adequate clinical information. Some histological features are atypical of these established entities and may indicate CVID, as may overlapping/changing histological patterns and/or few plasma cells in part of the gut. Awareness of the heterogenous clinical presentation and histopathological indicators of CVID may improve diagnosis.

PMID:39860504 | DOI:10.3390/jcm14020497

J Clin Med. 2025 Jan 9;14(2):363. doi: 10.3390/jcm14020363.

ABSTRACT

Background/Objectives: The nuclear factor (NF)-kB essential modulator (NEMO) has a crucial role in the NFκB pathway. Hypomorphic IKBKG pathogenic variants cause ectodermal dysplasia with immunodeficiency (EDA-ID) in affected males. However, heterozygous amorphic IKBKG variants could be responsible for Incontinentia Pigmenti (IP) in female carriers. Typically, IP patients do not exhibit immunodeficiency, although hypomorphic variants might lead to immunodeficiency in female IP patients. Here, we report the case of an IKBKG female carrier, with no IP but an unexpected picture of immunodeficiency. She had a positive family history for the same genetic condition. Methods: We performed immunological, molecular, and functional analysis to evaluate NEMO contribution. Results: The patient was healthy until the age of 25 when severe asthma and Hashimoto thyroiditis occurred. She had HLAB27-positive ankylosing spondylitis, non-tubercular mycobacteriosis, and pulmonary aspergillosis infections. We found CD19+ B cell lymphopenia and T cell subset alterations. Sanger sequencing revealed a heterozygous IKBKG variant at position +1 of the 5′ UTR of the gene which disrupted the normal pre-mRNA splicing. We observed a decreased NEMO protein expression, a reduced level of mRNA, and a defective NF-κB pathway. Conclusions: These findings suggest a possible correlation between the partial loss of NEMO function and the immunodeficiency observed in this patient. This case could expand our understanding of NEMO deficiency in female carriers.

PMID:39860371 | DOI:10.3390/jcm14020363