Research

Scand J Immunol. 2025 Jan;101(1):e13431. doi: 10.1111/sji.13431.

ABSTRACT

This study retrospectively analyzed the outcomes of 61 pediatric patients with inborn errors of immunity (IEI) who underwent hematopoietic stem cell transplantation (HSCT) between 2011 and 2023. Patients were categorized into primary immunodeficiency disorders (PIDD), primary immune dysregulation disorders (PIRD), and congenital defects of phagocyte number or function (CDP). Median ages at diagnosis and HSCT were 9 and 30 months, respectively. With a median follow-up of 51 months, the overall survival (OS) was 70%, with a 100-day post-transplant OS of 80%. Transplant-related mortality (TRM) was 29%, with rates of 42%, 22.5%, and 27% for PIRD, PIDD, and CDP, respectively. This study highlights the importance of early diagnosis and HSCT in improving survival for IEI patients, while also emphasizing the need for continuous improvements in transplant protocols to minimize TRM and enhance quality of life.

PMID:39781591 | DOI:10.1111/sji.13431

Allergy Asthma Clin Immunol. 2025 Jan 8;20(Suppl 3):76. doi: 10.1186/s13223-024-00938-z.

ABSTRACT

Primary immunodeficiencies (PID), now often referred to as inborn errors of immunity (IEI), are a large heterogeneous group of disorders that result from deficiencies in immune system development and/or function. IEIs can be broadly classified as disorders of adaptive immunity (e.g., combined or humoral immunodeficiencies) or of innate immunity (e.g., phagocyte and complement disorders). Although the clinical manifestations of IEIs are highly variable, traditionally many disorders involve an increased susceptibility to infection. Research in recent years has underscored how IEI can present with features other than infection such as: severe atopy, autoimmunity, autoinflammation, lymphoproliferation, and/or malignancy resulting from immune dysregulation. Early consultation with a clinical immunologist is essential, as timely diagnosis and treatment are imperative for preventing significant disease-associated morbidity and mortality. The treatment of IEIs is complex and generally requires both supportive and definitive strategies, including but not limited to, immunoglobulin replacement therapy, antibiotic prophylaxis, immune response modifiers, and hematopoietic stem cell transplantation. This article provides an overview of the major categories of IEIs and strategies for the appropriate diagnosis and management of these disorders.

PMID:39780212 | DOI:10.1186/s13223-024-00938-z

Pediatr Transplant. 2025 Feb;29(1):e70020. doi: 10.1111/petr.70020.

ABSTRACT

BACKGROUND: Disseminated mycobacterium poses a significant risk for patients with NEMO deficiency. Hematopoietic stem cell transplant (HSCT) corrects the NEMO defect in hematopoietic cells thus treating the immunodeficiency.

METHODS: We present a patient with NEMO deficiency who successfully underwent HSCT despite a disseminated Mycobacterium szulgai infection.

RESULTS: Despite successful engraftment and resolution of the mycobacterium infection, he developed inflammatory disease leading to his death.

CONCLUSION: HSCT does not cure all aspects of the NEMO protein defect and posttransplant inflammatory diseases involving nonhematopoietic cell types may manifest clinically.

PMID:39777821 | DOI:10.1111/petr.70020

Cardiology. 2025 Jan 8:1-13. doi: 10.1159/000543381. Online ahead of print.

ABSTRACT

INTRODUCTION: Primary immunodeficiency diseases (PIDs), are a growing group of rarely seen diseases. Various clinical conditions like autoimmunity, lymphoproliferative/malignant diseases, chronic lung and gastrointestinal system diseases have been identified which accompanies PIDs besides recurrent infections. However, there is a lack of information about accompanying cardiovascular diseases. We aimed to determine the frequency of cardiovascular diseases and arrhythmias in PID patients.

METHODS: 48 PID patients and 48 control group patients were included to this single-center, prospective controlled study. All patients underwent resting electrocardiogram, echocardiogram and 7-lead 24-hour ambulatory electrocardiogram (Holter) monitoring assessed by an experienced cardiologist.

RESULTS: Both supraventricular and ventricular extrasystoles were found to be statistically significantly higher in patient group in terms of frequency and sustained, non-sustained, and runs compared to control group. The median of total supraventricular extrasystoles was 8 (0-65) in patient group which was 0.5 (0-4.5) in control group (p<0.001) while the median of total ventricular extrasystoles was 2 (0-45.5) and 0 (0-2) in two groups, respectively (p=0.022). 18 patients (37.5%) had supraventricular and/or ventricular arrhythmias. The patient group had a statistically significantly higher systolic pulmonary artery pressure value compared to control group [20 (16-28) vs. 17.5 (15-25); p=0.036]. We found 7 patients had 13 structural heart diseases including second degree or above valve pathologies in patient group whereas none of the control group patients had these diseases (p=0.013).

CONCLUSION: With the positive findings of higher frequency and risk of arrhythmias and various structural heart diseases, we hope that our study will provide a new perspective on the management of PID patients, contributing positively to their survival and early prevention of cardiovascular comorbidities.

PMID:39778557 | DOI:10.1159/000543381

Allergy Asthma Clin Immunol. 2025 Jan 7;21(1):2. doi: 10.1186/s13223-024-00939-y.

ABSTRACT

BACKGROUND: Immunoglobulin replacement therapy (IgRT) is the current standard of care for primary antibody deficiency patients (majority of all primary immunodeficiency (PID) diseases), with growing real-world evidence supporting use for secondary immunodeficiency (SID) patients. Infusion methods and practices can affect patients’ satisfaction with their treatment and perception of their health-related quality of life.

METHODS: An online survey of US patients with PID and SID was conducted. This research investigates primarily the impact of two IgRT infusion methods, intravenous immunoglobulin therapy (IVIG) and subcutaneous immunoglobulin (SCIG), on the patient reported outcome (PRO) Life Quality Index (LQI) tool. Patient reported infusion time efficiency, physical and mental health (PROMIS GPH-2 and PROMIS GMH-2 respectively), patient acceptability of their symptom state (PASS), upper extremity disability (Quick DASH) and general health perception (via the GHP) are also investigated.

RESULTS: Responses of 990 patients (391 IVIG and 598 SCIG) were analyzed. The median total LQI score amongst SCIG patients (84.7) was higher than IVIG patients (81.9) (p < 0.001), and was significantly higher on 3 out of 4 sub-domains of the LQI. SCIG patients scored higher on items that are related to convenience and reported less interference with everyday life: “Are convenient”, “Are scheduled according to my convenience”, “Do not interfere with my work/school” and “Require very little time and cost”. However, there was no significant difference between the two patient cohorts on other, non-IG specific PROs (PASS, PROMIS GPH-2 and GMH-2 and Quick DASH). Patient reported time per infusion was lower for SCIG infusions than IVIG infusions (pre-infusion time; 22 min vs. 63 min, p < 0.001, infusion time; 120 min vs. 240 min, p < 0.001, post-infusion time; 9 min vs. 31 min, p < 0.001). IVIG patients also reported more interference with everyday life than SCIG patients (82 vs. 86, p < 0.001).

CONCLUSIONS: The significantly higher LQI scores for patients receiving SCIG than those receiving IVIG confirms existing evidence that substitution of SCIG for IVIG may favorably impact immunoglobulin specific perceptions of quality of life and treatment satisfaction for appropriately selected patients. Our evidence on infusion times indicates similar improvement may be possible on infusion time efficiency.

PMID:39773529 | DOI:10.1186/s13223-024-00939-y

Cells. 2024 Dec 16;13(24):2075. doi: 10.3390/cells13242075.

ABSTRACT

Natural aging and age-related diseases involve the acceleration of replicative aging, or senescence. Multiple proteins are known to participate in these processes, including the promyelocytic leukemia (PML) protein, which serves as a core component of nuclear-membrane-less organelles known as PML nuclear bodies (PML-NBs). In this work, morphological changes in PML-NBs and alterations in PML protein localization at the transition of primary fibroblasts to a replicative senescent state were studied by immunofluorescence. The fibroblasts were obtained from both healthy donors and donors with premature aging syndromes (ataxia-telangiectasia and Cockayne syndrome). Our data showed an increase in both the size and the number of PML-NBs, along with nuclear enlargement in senescent cells, suggesting these changes could serve as potential cellular aging markers. Bioinformatic analysis demonstrated that 30% of the proteins in the PML interactome and ~45% of the proteins in the PML-NB predicted proteome are directly associated with senescence and aging processes. These proteins are hypothesized to participate in post-translational modifications and protein sequestration within PML-NBs, thereby influencing transcription factor regulation, DNA damage response, and negative regulation of apoptosis. The findings confirm the significant role of PML-NBs in cellular aging processes and open new avenues for investigating senescence mechanisms and age-associated diseases.

PMID:39768166 | DOI:10.3390/cells13242075

Pathogens. 2024 Dec 20;13(12):1128. doi: 10.3390/pathogens13121128.

ABSTRACT

Individuals with certain primary immunodeficiency disorders (PID) may be unable to clear poliovirus infection after exposure to oral poliovirus vaccine (OPV). Over time, vaccine-related strains can revert to immunodeficiency-associated vaccine-derived poliovirus (iVDPVs) that can cause paralysis in the patient and potentially spread in communities with low immunity. We reviewed the efforts for detection and management of PID patients with iVDPV infections and the epidemiology through an analysis of 184 cases reported to the World Health Organization (WHO) during 1962-2024 and a review of polio program and literature reports. Most iVDPV patients (79%) reported in the WHO Registry were residents in middle-income countries and almost half (48%) in the Eastern Mediterranean Region. Type 2 iVDPV was most frequently isolated (53%), but a sharp decline was observed after the switch to bivalent OPV in 2016, with only six cases reported during 2017-2024 compared to 63 during 2009-2016. Patients with common variable immunodeficiency have longer excretion of iVDPV than with other PID types. Implementation of sensitive sentinel surveillance to detect cases of iVDPV infection in high-risk countries and offer antiviral treatment to patients is challenged by competition with other health priorities and regulatory hurdles to the compassionate use of investigational antiviral drugs.

PMID:39770387 | DOI:10.3390/pathogens13121128

Microorganisms. 2024 Dec 23;12(12):2669. doi: 10.3390/microorganisms12122669.

ABSTRACT

Campylobacteriosis is a leading cause of infectious diarrhea and foodborne illness worldwide. Campylobacter infection is primarily transmitted through the consumption of contaminated food, especially uncooked meat, or untreated water; contact with infected animals or contaminated environments; poultry is the primary reservoir and source of human transmission. The clinical spectrum of Campylobacter jejuni/coli infection can be classified into two distinct categories: gastrointestinal and extraintestinal manifestations. Late complications are reactive arthritis, Guillain-Barré syndrome, and Miller Fisher syndrome. In the pediatric population, the 0-4 age group has the highest incidence of campylobacteriosis. Regarding the use of specific antimicrobial therapy, international guidelines agree in recommending it for severe intestinal infections. Host factors, including malnutrition, immunodeficiency, and malignancy, can also influence the decision to treat. The Centers for Disease Control and Prevention (CDC) has identified antibiotic resistance in Campylobacter as a ‘significant public health threat’ due to increasing resistance to FQs or macrolides. Although numerous vaccines have been proposed in recent years to reduce the intestinal colonization of poultry, none have shown sufficient efficacy to provide a definitive solution.

PMID:39770871 | DOI:10.3390/microorganisms12122669

J Clin Immunol. 2025 Jan 6;45(1):65. doi: 10.1007/s10875-024-01850-2.

ABSTRACT

Receptor Interacting Serine/Threonine Kinase 1 (RIPK1) is widely expressed and integral to inflammatory and cell death responses. Autosomal recessive RIPK1-deficiency, due to biallelic loss of function mutations in RIPK1, is a rare inborn error of immunity (IEI) resulting in uncontrolled necroptosis, apoptosis and inflammation. Although hematopoietic stem cell transplantation (HSCT) has been suggested as a potential curative therapy, the extent to which disease may be driven by extra-hematopoietic effects of RIPK1-deficiency, which are non-amenable to HSCT, is not clear. We present a multi-centre, international review of an additional 5 RIPK1-deficient children who underwent HSCT. All patients presented with very early onset inflammatory bowel disease, 2 also suffered from inflammatory arthritis. Median age at transplant was 3 years (range 1-5 years); 1 received matched sibling marrow, 1 matched unrelated peripheral blood stem cells (PBSC), 2 TCRαβ/CD19-depleted PBSC from maternal-haploidentical donors, and 1 had TCRαβ/CD19-depleted PBSC from a mismatched unrelated donor. All received reduced-toxicity conditioning, based on treosulfan (n = 4) or busulfan (n = 1); 1 patient underwent a successful second transplant following autologous reconstitution. Four of five patients (80%) survived; 1 child died due to multi-drug resistant pseudomonas infection and multi-organ failure. With a median duration of 14 months follow-up, 2 survivors were disease-free, and 2 had substantially improving enteropathy. These findings demonstrated that HSCT is a potential curative therapy for RIPK1-deficiency.

PMID:39762600 | DOI:10.1007/s10875-024-01850-2

J Nippon Med Sch. 2024;91(6):574-578. doi: 10.1272/jnms.JNMS.2024_91-606.

ABSTRACT

An infant was diagnosed as having X-linked agammaglobulinemia (XLA) at age 3 months and was receiving immunoglobulin replacement therapy. He developed SARS-CoV-2 infection at age 7 months and was treated with intravenous immunoglobulin, remdesivir, and dexamethasone. His respiratory symptoms improved quickly, and the infection resolved. Viral disappearance was confirmed via PCR, and the result of a SARS-CoV-2 test was negative on day 67 of illness, as a result of antiviral therapy. Immunoglobulin administered to the patient did not contain anti-SARS-CoV-2 antibodies, and no seroconversion of anti-SARS-CoV-2 antibodies was observed after healing. These findings suggest that humoral immunity did not contribute to infection in our patient. Thus, the importance of cellular immunity against COVID-19 was confirmed. In the future, it is hoped that testing companies will be able to use the ELISPOT assay to check cellular immunity in order to confirm the effectiveness of vaccines and the history of infection.

PMID:39756947 | DOI:10.1272/jnms.JNMS.2024_91-606