Manish Butte

Malays J Med Sci. 2025 Feb;32(1):141-153. doi: 10.21315/mjms-08-2024-608. Epub 2025 Feb 28.

ABSTRACT

BACKGROUND: This study aimed to determine the knowledge and attitude of the Malaysian public towards blood donation during the COVID-19 pandemic.

METHOD: This cross-sectional study utilised an online questionnaire to survey 409 Malaysians between 18 to 60 years old who were non-healthcare workers recruited via convenient snowball sampling. Data were analysed descriptively and via multiple logistic regression.

RESULTS: About half (49.2%) of the participants have good knowledge of blood donation while 71.2% of them reported a positive attitude. Gender and blood donation experience were significantly associated with knowledge of blood donation. However, only gender was associated with attitude concerning blood donation. Gender, age, income and donation experience were significantly related to the perception of blood need. No factor was identified as significantly associated with the perception of blood donation risk. The majority of the participants quoted the main reason for blood donation as to save lives.

CONCLUSION: Most of the participants in this study showed a good knowledge and positive attitude towards blood donation. Gender, age, income and donation experience were the main associated factors. Based on these findings, future recruitment approaches for blood donors should target these identified groups, whereas promotional campaigns should be held among populations with poorer knowledge and attitudes towards blood donation, i.e., males, non-donors, younger populations and those with lower income.

PMID:40417200 | PMC:PMC12097151 | DOI:10.21315/mjms-08-2024-608

Front Immunol. 2025 May 9;16:1596963. doi: 10.3389/fimmu.2025.1596963. eCollection 2025.

ABSTRACT

INTRODUCTION: The Bacillus Calmette-Guérin (BCG) vaccine is widely used to prevent tuberculosis but is associated with significant complications in patients with severe combined immunodeficiency (SCID). Considering the high incidence of SCID in Saudi Arabia, the Ministry of Health revised its national vaccination schedule in 2019, postponing BCG administration from birth to 6 months of age, aiming to enable time for the diagnosis of primary immunodeficiency diseases before vaccination. This study evaluated the consequences of this policy change on the incidence of BCG-related complications in SCID patients.

METHODS: This retrospective study included 178 SCID patients diagnosed at King Faisal Specialist Hospital and Research Center, Riyadh, between 2015 and 2023. Patients were divided into two cohorts: Era 1 (2015-2019), when BCG vaccination was administered at birth, and Era 2 (2019-2023), when BCG vaccination was administered at 6 months of age. Data on demographics, clinical presentations, BCG-related complications, genetic testing, treatment, and outcomes were analyzed.

RESULTS: A total of 49 SCID patients developed BCGitis, of which 65.3% experienced disseminated disease. The incidence of BCG-related complications dropped significantly after the policy change, from 46.1% in Era 1 to 2.6% in Era 2. Patients required stem cell transplantation and a median of 17.6 months of anti-mycobacterial therapy. The crude mortality rate was high (36.7%; 18/49), with 66.7% (12/18) of these fatalities linked to disseminated BCGitis.

CONCLUSIONS: Postponing BCG vaccination to 6 months of age significantly decreases the incidence of BCG-related complications in SCID patients and highlights the importance of tailoring vaccination schedules for high-risk populations. Early newborn screening and timely diagnosis of immunodeficiencies are essential to further minimize complications. The revised vaccination policy of Saudi Arabia provides a model for optimizing immunization strategies in regions with a high prevalence of inborn errors of immunity.

PMID:40416983 | PMC:PMC12098544 | DOI:10.3389/fimmu.2025.1596963

Eur J Immunol. 2025 May;55(5):e202451382. doi: 10.1002/eji.202451382.

ABSTRACT

The innate immune system relies on nucleic acid (NA) sensors to detect viral infections and trigger type I interferon (IFN-I) responses, which are crucial for antiviral defense. NA pattern recognition receptors detect viral RNA or DNA within various cellular compartments, initiating antiviral signaling pathways. However, inherited deficiencies in these NA sensing mechanisms can result in increased susceptibility to severe viral infections. This review explores key genetic mutations affecting NA sensing and IFN-I pathways that predispose individuals to life-threatening viral diseases, including herpesviruses, respiratory viruses, enteroviruses, arboviruses, and vaccine-strain disseminated viral diseases. The identification of these monogenic defects in individuals afflicted by severe viral infections, along with the observed incomplete penetrance of these mutations, highlight the intricate interplay of the host’s intrinsic, innate, and adaptive immune response with invading viral pathogens. These insights into the molecular basis of antiviral immunity not only underscore the clinical challenges associated with viral susceptibility but also offers the opportunity for personalized treatment strategies, including genetic screening, tailored vaccination protocols, and targeted antiviral therapies.

PMID:40415206 | DOI:10.1002/eji.202451382

Curr Opin Immunol. 2025 May 24;95:102565. doi: 10.1016/j.coi.2025.102565. Online ahead of print.

ABSTRACT

Autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis are well-defined autoimmune liver diseases, the pathophysiology of which remains enigmatic. While major therapeutic advances have been achieved for many other autoimmune diseases, precision therapy for these diseases has lagged. For example, limited data exist on the use of innovative drugs targeting the immune system, such as monoclonal antibodies that block immune checkpoint, mRNA vaccines, the influence of infections, the microbiome, and drugs on loss of tolerance in liver autoimmunity. The knowledge on recent radiological techniques, on the expanding role of artificial intelligence in medicine, and on the relationship between the pediatric and adult phenotypes also urgently needs to be advanced in liver autoimmunity. Increased patient involvement focusing on individual symptom burden is also crucial for improving long-term quality of treatment. The fourth Swiss Autoimmune Liver Disease Meeting provided a unique interdisciplinary platform for experts and patients to discuss critical gaps. This opinion paper highlights the discussions on unmet needs and potential solutions in autoimmune liver diseases.

PMID:40414140 | DOI:10.1016/j.coi.2025.102565

Lancet Rheumatol. 2025 May 21:S2665-9913(25)00034-7. doi: 10.1016/S2665-9913(25)00034-7. Online ahead of print.

ABSTRACT

BACKGROUND: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently described autoinflammatory disorder with little therapeutic evidence. We compared treatment outcomes of targeted therapies versus prednisolone alone in the largest UK cohort of patients with VEXAS syndrome to date.

METHODS: In this retrospective cohort study, we analysed the outcomes of targeted therapies in patients with VEXAS syndrome in six tertiary referral centres across the UK between July 22, 2014, and Oct 19, 2024. The inclusion criteria were genetically confirmed VEXAS syndrome and receipt of at least one targeted therapy or prednisolone alone. Patients without clinical information at all timepoints after baseline were excluded. Data collection forms were used to record clinical and biochemical data at the following timepoints: time of diagnosis, initiation of treatment, and follow-up at 3 months, 6 months, and 12 months from the initiation of treatment (±28 days). Laboratory parameters, including C-reactive protein (CRP) and haemoglobin, and glucocorticoid doses were collected at each timepoint and compared between timepoints. Primary outcomes were complete response (ie, clinical remission, CRP ≤10 mg/L, and prednisolone ≤10 mg per day) and partial response (ie, clinical remission with ≥50% reductions in both CRP and glucocorticoid dose from baseline) to treatment. Treatment discontinuation and adverse events were documented for each treatment. Due to the high prevalence of cytopenias in VEXAS syndrome, these were only recorded as adverse events when necessitating treatment change. People with lived experience were not involved in the study.

FINDINGS: We analysed 71 targeted therapies in 59 patients with genetically confirmed VEXAS syndrome. Of the 59 patients, 58 (98%) were male and one (2%) was female, with a mean age of 71 years (SD 8), and 27 (46%) had myelodysplastic syndrome. The treatments included tocilizumab (n=19), anakinra (n=13), azacitidine (n=13), baricitinib (n=11), and prednisolone only (n=10). At 6 months, in those who continued therapy, ten (91%) of 11 patients receiving azacitidine showed a response (three [27%] complete responses), as well as did seven (64%) of 11 receiving tocilizumab (four [36%] complete responses), three (100%) of three receiving anakinra (one [33%] complete response), and two (40%) of five receiving baricitinib (no complete responses). Although all patients who tolerated anakinra had a response, the discontinuation rate was high (eight [62%] of 13), mostly due to severe injection-site reactions (n=5). Patients were more likely to respond to azacitidine than to other therapies at 6 months (risk ratio 2·47, 95% CI 1·18-5·20; p=0·018). Absence of fever or thromboembolism at diagnosis was associated with better outcomes. By 6 months, median CRP concentrations had decreased in patients receiving tocilizumab (from 30 mg/L [IQR 13-45] to 4 mg/L [3-37]) or anakinra (from 18 mg/L [11-52] to 2 mg/L [1-28]), whereas azacitidine showed the greatest increase in haemoglobin (from mean concentration 104 g/L [SD 17·5] to 120 g/L [14·4]). 28 (39%) of 71 treatments were discontinued, most commonly due to serious adverse events (12 [17%]) and death (nine [13%]). Infections were most frequent with azacitidine (eight [62%] of 13) and tocilizumab (nine [47%] of 19).

INTERPRETATION: In this UK cohort of patients with VEXAS syndrome, azacitidine and tocilizumab showed superior effectiveness compared with anakinra, baricitinib, and prednisolone only. Treatment selection should consider individual risk factors and tolerability. Prospective studies are needed to confirm optimal treatment strategies and develop standardised protocols.

FUNDING: None.

PMID:40412417 | DOI:10.1016/S2665-9913(25)00034-7

Immunol Res. 2025 May 24;73(1):86. doi: 10.1007/s12026-025-09642-5.

ABSTRACT

Stromal interaction molecule 1 (STIM1) is a transmembrane protein located in the endoplasmic and sarcoplasmic reticulum, where it plays a crucial role in activating calcium release-activated calcium (CRAC) channels. It functions as a calcium (Ca²⁺) sensor within the endoplasmic reticulum (ER), triggering CRAC channel opening and allowing calcium entry-mechanisms essential for maintaining intracellular calcium homeostasis. Mutations in the STIM1 gene that impair calcium signaling can disrupt both T cell and muscle cell function, leading to combined immunodeficiency and congenital myopathy. Here, we describe a 9-year-old boy with these clinical features, who was found to carry a previously undescribed mutation in the STIM1 gene. The patient presented with recurrent pneumonia, blood-streaked diarrhea, eczema, muscle weakness, and failure to thrive. Whole exome sequencing identified a novel homozygous missense variant in STIM1 (c.584T > C | p.Leu195Pro), considered likely pathogenic. This classification was supported by high Combined Annotation Dependent Depletion (CADD) and Rare Exome Variant Ensemble Learner (REVEL) scores of 29.8 and 0.89, respectively. Homozygosity of the mutation was confirmed using PCR-Sanger sequencing. This case highlights a novel homozygous STIM1 variant in a child with combined immunodeficiency and congenital myopathy. The clinical presentation is consistent with previously reported phenotypes associated with STIM1 deficiency.

PMID:40411647 | DOI:10.1007/s12026-025-09642-5

BMC Rheumatol. 2025 May 23;9(1):57. doi: 10.1186/s41927-025-00508-9.

ABSTRACT

BACKGROUND AND OBJECTIVE: In recent years, many studies have been conducted on the possible link between rheumatologic diseases and inborn errors of immunity. Rheumatologic diseases may occur as manifestations of an underlying immunodeficiency disorder, and may appear before the more-common infectious manifestations more typically seen in immunodeficiency disorders. In this study, we have attempted to study such symptoms and uncover their relationship with inborn errors of immunity.

METHODOLOGY: In this retrospective descriptive-analytical study, 381 cases of IEIs in children that were referred to Mofid Children’s Hospital clinic between 2015 and 2019 were evaluated for eligibility to be enrolled in the study. Of these patients, 20 that had confirmed rheumatologic diagnoses were entered into the study. Patients’ demographic and medical data, including age at disease onset, age at diagnosis and type of diagnosed rheumatologic and immunodeficiency disorders, parental consanguinity rate, and relevant laboratory findings were retrieved for study and analyzed.

RESULTS: Among 20 eligible patients, half of which were female and half were male, the average age at disease onset, average age at diagnosis of the underlying immunodeficiency disease and average age at diagnosis of the rheumatologic disease were 2.98 ± 1.56, 5.26 ± 3.45 and 3.58 ± 2.97, respectively. JIA made up 10 of the observed rheumatic diseases (“the JIA group”); the remaining 10 patients included SLE (3), FMF (2), juvenile dermatomyositis (2), MCTD (1), GPA (1) and reactive arthritis (1) (“the non-JIA group”). As for the underlying immunodeficiency disorders, CID was seen in 8 patients, followed by CVID (5), XLA (4), SIgAD (2) and CGD (1). The average age at onset of the disease and the average age at diagnosis of the rheumatologic disease were significantly lower in the JIA group than in the non-JIA group (p < 0.05).

CONCLUSIONS: A plethora of rheumatologic manifestations may be observed in patients with IEIs; such manifestations should be actively sought out and treated in IEI patients.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40410798 | DOI:10.1186/s41927-025-00508-9

J Clin Immunol. 2025 May 23;45(1):97. doi: 10.1007/s10875-025-01890-2.

ABSTRACT

PURPOSE: There are few reports of renal involvement in Common Variable Immunodeficiencies (CVID) and, when present, is due to infections, inflammation, or treatments. The aim of this study was evaluating the prevalence of chronic kidney disease (CKD) and to identify CVID-related clinical, laboratory and therapeutic features inducing it.

METHODS: A multicenter observational retrospective study on 367 adult CVID patients from five Italian Referral Centers for Primary Immunodeficiency.

RESULTS: CKD was identified in 23 (6.27%) patients that were older (p < 0.001), had arterial hypertension (p < 0.001), diabetes (p = 0.002), dyslipidemia (p = 0.002), presented different ultrasound abnormalities (p < 0.001) and received predominantly intravenous immunoglobulins (IVIG) (p = 0.016). Regarding CVID infectious and non-infectious manifestations, CKD patients presented a higher frequency of COPD (p = 0.008). In the CKD group, the median absolute count of total lymphocytes (p = 0.015), the percentage of total B (p = 0.028) and transitional B cells (p = 0.008) were lower. By binomial logistic regression analysis adjusted for age, CKD patients tend to develop autoimmune cytopenia, had lower B cells percentage, increased Neutrophil-to-lymphocyte ratio and received more frequently trimethoprim-sulfamethoxazole antibiotic prophylaxis. By multivariate analysis, only autoimmune cytopenia was independently associated with CKD.

CONCLUSION: The prevalence of CKD in CVID is due to aging, age-related comorbidities, disease-related immune dysregulation and inflammation. Our results suggest evaluating renal function in all CVID patients, and mostly in those with a higher “inflammatory” burden.

PMID:40407942 | DOI:10.1007/s10875-025-01890-2

Cureus. 2025 Apr 22;17(4):e82763. doi: 10.7759/cureus.82763. eCollection 2025 Apr.

ABSTRACT

Introduction Primary central nervous system lymphoma (PCNSL) is a rare type of malignant tumor. Due to the rapidly progressive nature of PCNSL, early diagnosis is important, and imaging plays a key role in this process. In particular, N-isopropyl-p(123I)iodoamphetamine (¹²³I-IMP) single-photon emission computed tomography (SPECT) is useful for PCNSL diagnosis because it shows a high accumulation, which distinguishes the lesion from other brain tumors. Recently, PCNSL has been increasingly observed in immunosuppressed patients, including those who have undergone organ transplantation and those who are receiving treatment for acquired immunodeficiency syndrome. These conditions may alter the tumor microenvironment, thereby potentially influencing ¹²³I-IMP accumulation. The current study aimed to validate how immunosuppression affects the diagnostic imaging of PCNSL using ¹²³I-IMP SPECT. Materials and methods This study included 12 patients diagnosed with PCNSL based on surgical specimens, all of whom underwent early and delayed ¹²³I-IMP SPECT imaging. The patients were divided into the immunosuppressed and non-immunosuppressed groups. The immunosuppressed group consisted of three patients who received steroids or immunosuppressants after kidney transplantation. Seven tumors from the three patients in the immunosuppressed group and nine tumors from the nine patients in the non-immunosuppressed group were compared. Early and delayed SPECT images were obtained, and the regions of interest were defined by fusing SPECT with magnetic resonance imaging. The tumor-to-cerebellum (T/C) ratio was calculated, and statistical analysis was performed using the Mann-Whitney U test. Results The immunosuppressed group had a significantly lower T/C ratio on the early ¹²³I-IMP SPECT images than the non-immunosuppressed group (0.57 ± 0.14 vs 0.83 ± 0.14, p < 0.01). The immunosuppressed group also had a significantly lower accumulation on the delayed images than the non-immunosuppressed group (0.84 ± 0.16 vs. 1.22 ± 0.10, p < 0.001). The T/C ratio showed a statistically significant increase from the early to delayed images in both the immunosuppressed and non-immunosuppressed groups (p < 0.01, p < 0.001). Conclusions The immunosuppressed group had a significantly lower ¹²³I-IMP accumulation in the early and delayed images than the non-immunosuppressed group. Based on this finding, an immunosuppressed state strongly influences the ¹²³I-IMP uptake in PCNSL. Thus, the presence or absence of an immunosuppressed state should be considered when diagnosing PCNSL using ¹²³I-IMP SPECT.

PMID:40406751 | PMC:PMC12096338 | DOI:10.7759/cureus.82763

Qatar Med J. 2025 Mar 21;2025(1):14. doi: 10.5339/qmj.2025.14. eCollection 2025.

ABSTRACT

BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency due to alterations in the oxidative metabolism of phagocytic cells. This condition is characterized by serious and recurrent infections caused by pyogenic bacteria, particularly Staphylococcus aureus, and fungal pathogens such as Aspergillus. These infections are associated with granuloma formation and inflammatory manifestations.The aim of our study was to report the clinical characteristics, microbiological aspects and outcomes, and prognosis of a cohort comprising 42 Moroccan patients suffering from CGD.

METHODS: A total of 42 patients were diagnosed for family history, consanguinity, and both clinical and laboratory findings.The diagnosis was confirmed by assessing neutrophil oxidative burst activity, using either the nitroblue tetrazolium (NBT) test or the dihydrorhodamine (DHR) test.

RESULTS: The cohort comprised children from 34 different families, including 12 siblings. The age of onset ranged from 4 days to 13 years, with the diagnosis being established between the ages of 25 days and 13 years. The predominant clinical manifestations were skin infections, lymphadenopathy, pneumonia, BCGitis, liver abscess, pulmonary aspergillosis, and inflammatory colitis. The most frequently isolated germs were Aspergillus, Serratia, and Staphylococcus. Among the total of 42 patients, 17 fatalities occurred, with aspergillosis being identified as the primary cause of their deaths.

CONCLUSIONS: In this study, the clinical characteristics and isolated microorganisms correspond to the pathogens known to be important in CGD. Lung infections represent the most prevalent complication and significantly contribute to high mortality rates, particularly in the case of Aspergillus pneumonia, which is known for its tendency to disseminate. Additionally, BCGitis has been frequently observed in countries where the BCG (Bacille Calmette-Guérin) vaccination is routinely administered. Enterocolitis emerges as the most common inflammatory complication in clinical settings. Unfortunately, CGD remains largely unknown in Morocco, highlighting the urgent need to raise awareness among doctors. This increased awareness could facilitate early diagnosis and improve patient prognosis.

PMID:40401231 | PMC:PMC12092978 | DOI:10.5339/qmj.2025.14