Manish Butte

Ther Adv Allergy Rhinol. 2023 Mar 14;14:27534030231156206. doi: 10.1177/27534030231156206. eCollection 2023 Jan-Dec.

ABSTRACT

Vaccinations for pathogenic organisms have been utilized for decades in both the protection and diagnosis of immunodeficiency patients. Some of these immunodeficient patients may not create an adequate response to vaccination, although some who have significant aberrancies in their immune system may surprisingly create antibodies to immunizations. We present a patient with a large Ig heavy chain deletion (severe deficiency of serum IgG1, IgG2, IgG4, and IgA1) that showed a considerable response (presumably through IgG3) after the Pfizer BioNTech COVID-19 vaccination. This finding in this unique immunodeficient patient warrants further research into alternate antibody response pathways against COVID-19.

PMID:36968252 | PMC:PMC10035523 | DOI:10.1177/27534030231156206

Clin Immunol. 2023 Mar 24:109302. doi: 10.1016/j.clim.2023.109302. Online ahead of print.

ABSTRACT

Up to 25% of the patients with inborn errors of immunity (IEI) also exhibit immunodysregulatory features. The association of immune dysregulation and immunodeficiency may be explained by different mechanisms. The understanding of mechanisms underlying immune dysregulation in IEI has paved the way for the development of targeted treatments. In this review article, we will summarize the mechanisms of immune tolerance breakdown and the targeted therapeutic approaches to immune dysregulation in IEI.

PMID:36967025 | DOI:10.1016/j.clim.2023.109302

PLOS Glob Public Health. 2023 Feb 23;3(2):e0001572. doi: 10.1371/journal.pgph.0001572. eCollection 2023.

ABSTRACT

Reducing mortality among COVID-19 cases is a major challenge for most health systems worldwide. Estimating the risk of preexisting comorbidities on COVID-19 mortality may promote the importance of targeting at-risk populations to improve survival through primary and secondary prevention. This study was conducted to explore the contribution of exposure to some chronic diseases on the mortality of COVID-19. This was a case control study. The data were collected from the records of all patients hospitalised at Bafoussam Regional Hospital (BRH) from March 2020 to December 2021. A grid was used to extract data on patient history, case management and outcome of hospitalised patients. We estimated the frequency of each common chronic disease and assessed the association between suffering from all and each chronic disease (Diabetes or/and Hypertension, immunodeficiency condition, obesity, tuberculosis, chronic kidney disease) and fatal outcome of hospitalised patients by estimating crude and adjusted odd ratios and their corresponding 95% confidence intervals (CI) using time to symptom onset and hospital admission up to three days, age range 65 years and above, health professional worker and married status as confounder’s factors. Of 645 included patients, 120(20.23%) deaths were recorded. Among these 645 patients, 262(40.62%) were males, 128(19.84%) aged 65 years and above. The mean length of stay was 11.07. On admission, 204 (31.62%) patients presented at least one chronic disease. The most common chronic disease were hypertension (HBP) 73(11.32%), followed by diabetes + HBP 62 (9.61%), by diabetes 55(8.53%) and Immunodeficiency condition 14(2.17%). Diabetes and Diabetes + HBP were associated with a higher risk of death respectively aOR = 2.71[95%CI = 1.19-6.18] and aOR = 2.07[95% CI = 1.01-4.23] but HBP did not significantly increased the risk of death. These results suggest that health authorities should prioritize these specific group to adopt primary and secondary preventive interventions against SARS-CoV-2 infection.

PMID:36963083 | DOI:10.1371/journal.pgph.0001572

J Immunol. 2023 Mar 24:ji2200818. doi: 10.4049/jimmunol.2200818. Online ahead of print.

ABSTRACT

Autosomal recessive PRKCD deficiency has previously been associated with the development of systemic lupus erythematosus in human patients, but the mechanisms underlying autoimmunity remain poorly understood. We introduced the Prkcd G510S mutation that we previously associated to a Mendelian cause of systemic lupus erythematosus in the mouse genome, using CRISPR-Cas9 gene editing. PrkcdG510S/G510S mice recapitulated the human phenotype and had reduced lifespan. We demonstrate that this phenotype is linked to a B cell-autonomous role of Prkcd. A detailed analysis of B cell activation in PrkcdG510S/G510S mice shows an upregulation of the PI3K/mTOR pathway after the engagement of the BCR in these cells, leading to lymphoproliferation. Treatment of mice with rapamycin, an mTORC1 inhibitor, significantly improves autoimmune symptoms, demonstrating in vivo the deleterious effect of mTOR pathway activation in PrkcdG510S/G510S mice. Additional defects in PrkcdG510S/G510S mice include a decrease in peripheral mature NK cells that might contribute to the known susceptibility to viral infections of patients with PRKCD mutations.

PMID:36961448 | DOI:10.4049/jimmunol.2200818

Laryngoscope. 2023 Mar 24. doi: 10.1002/lary.30672. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to explore diet patterns in children with tympanostomy tube placement (TTP) complicated by postoperative tympanostomy tube otorrhea.

STUDY DESIGN: Cross-sectional survey and retrospective cohort study.

METHODS: Caregivers of children (0-12 years old), at a tertiary-care pediatric hospital who underwent TTP within 6 months to 2 years prior to enrollment were included. Children with a history of Down syndrome, cleft palate, craniofacial syndromes, known immunodeficiency, or a non-English-speaking family were excluded. Our primary outcome variable was the number of otorrhea episodes. The primary predictor was diet patterns, particularly dessert intake, which was captured through a short food questionnaire.

RESULTS: A total of 286 participants were included in this study. The median age was 1.8 years (IQR, 1.3, 2.9). A total of 174 (61%) participants reported at least one episode of otorrhea. Children who consumed dessert at least two times per week had a higher risk of otorrhea compared to children who consumed one time per week or less (odds ratio [OR], 3.22, 95% Confidence Interval [CI]: 1.69, 6.12). The odds ratio increase continued when considering more stringent criteria for otorrhea (multiple episodes or one episode occurring 4 weeks after surgery), with a 2.33 (95% CI: 1.24, 4.39) higher odds of otorrhea in children with dessert intake at least 2 times per week.

CONCLUSIONS: Our pilot data suggest that episodes of otorrhea among children with TTP were associated with more frequent dessert intake. Future studies using prospectively administered diet questionnaires are necessary to confirm these findings.

LEVEL OF EVIDENCE: 4 Laryngoscope, 2023.

PMID:36960887 | DOI:10.1002/lary.30672

J Clin Immunol. 2023 Mar 24. doi: 10.1007/s10875-023-01474-y. Online ahead of print.

ABSTRACT

PURPOSE: Chronic sleep issues can lead to poor quality of life and increased mortality and patients with chronic health conditions often report impaired sleep quality. Higher levels of fatigue have been identified in patients diagnosed with inborn errors of immunity (or primary immunodeficiency diseases). This research sought to better understand perceived sleep quality in individuals diagnosed with IEI.

METHODS: A survey, which included the validated Sleep Quality Scale, was shared across multiple social media groups for individuals with a diagnosis of IEI.

RESULTS: Most of the participants were White/Caucasian females, between the ages of 30 and 74 years. The results of the Sleep Quality Scale suggest that this sample of individuals has moderate impairment of their sleep quality (71.8%), with a mean score of 43.0 (SD = 13.1). When comparing the results of the SQS to other patient populations and healthy control groups, the participants in this study had a poorer sleep quality score. Associations were identified between sleep quality and age, hours of sleep per night, time awake at night, times awake to urinate, attempted daytime naps, chronic pain, and mental health diagnoses.

CONCLUSION: This survey suggests that individuals with inborn errors of immunity have a moderate degree of perceived impairment in sleep quality. Healthcare providers are strongly encouraged to incorporate sleep quality screening in their routine assessments of patients with a diagnosis of Inborn Error of Immunity. Patients who are identified as having impaired sleep quality should be referred for further testing and interventions.

PMID:36959490 | DOI:10.1007/s10875-023-01474-y

Front Pediatr. 2023 Mar 6;11:1103726. doi: 10.3389/fped.2023.1103726. eCollection 2023.

ABSTRACT

BACKGROUND: Patients with primary immunodeficiency disorders (PIDs) often suffer from recurrent infections because of their inappropriate immune response to both common and less common pathogens. These patients may present with unique and severe cutaneous infectious manifestations that are not common in healthy individuals and may be more challenging to diagnose and treat.

OBJECTIVE: To describe a cohort of patients with PIDs with atypical presentations of skin infections, who posed a diagnostic and/or therapeutic challenge.

METHODS: This is a retrospective study of pediatric patients with PID with atypical presentations of infections, who were treated at the immunodeficiency specialty clinic and the pediatric dermatology clinic at the Sheba Medical Center between September 2012 and August 2022. Epidemiologic data, PID diagnosis, infectious etiology, presentation, course, and treatment were recorded.

RESULTS: Eight children with a diagnosis of PID were included, five of whom were boys. The average age at PID diagnosis was 1.7 (±SD 3.2) years. The average age of cutaneous infection was 6.9 (±SD 5.9) years. Three patients were born to consanguineous parents. The PIDs included the following: common variable immunodeficiency, severe combined immunodeficiency, DOCK8 deficiency, ataxia telangiectasia, CARD11 deficiency, MALT1 deficiency, chronic granulomatous disease, and a combined cellular and humoral immunodeficiency syndrome of unknown etiology. The infections included the following: ulcerative-hemorrhagic varicella-zoster virus (two cases) atypical fungal and bacterial infections, resistant Norwegian scabies, giant perianal verrucae (two cases), and diffuse molluscum contagiosum.

CONCLUSIONS: In this case series, we present unusual manifestations of infectious skin diseases in pediatric patients with PID. In some of the cases, recognition of the infectious process prompted life-saving treatment. Increasing familiarity with these dermatological manifestations, as well as keeping a high index of suspicion, is important to enabling early diagnosis of cutaneous infections in PIDs and initiation of prompt suitable treatment.

PMID:36950172 | PMC:PMC10026180 | DOI:10.3389/fped.2023.1103726

EJVES Vasc Forum. 2023 Mar 1;58:23-27. doi: 10.1016/j.ejvsvf.2023.02.003. eCollection 2023.

ABSTRACT

INTRODUCTION: Intravesical Bacillus Calmette-Guerin (BCG) is an effective treatment for in situ bladder carcinomas; however, extravesical BCG infection may occur in remote organs in patients with underlying primary immunodeficiency and is a potentially serious complication in 3-5% of cases. It includes granulomatous pneumonia, hepatitis as well as specific dermatological, ophthalmic, and haematopoietic manifestations. Diagnosis is difficult and often based on high clinical suspicion as in many cases Mycobacterium bovis is not isolated. This report presents a rare case of BCGaortitis treated in a tertiary care centre.

REPORT: A 74 year old man, with a history of bladder cancer treated with BCG therapy over a year ago, presented with malaise, abdominal pain, anorexia, and significant weight loss for several months associated with acute on chronic renal failure and a tender aneurysm. He was diagnosed with hepatic BCGitis and pararenal BCGaortitis. He was considered too high risk for open surgery after a multidisciplinary team meeting and was treated with a four vessel physician modified endograft (PMEG) and antituberculous therapy. At seven month follow up, he was clinically well and control computed tomography showed a patent endograft with complete exclusion of the aortic aneurysm.

DISCUSSION: Infectious BCG complications after intravesical BCG administration for in situ bladder carcinomas can lead to severe early and late complications. In the present case, the patient presented with both liver and aortic BCG infection. The lack of positive microbiological data should not discourage clinicians from considering BCG infection even if several months have passed since the last BCG instillation.

PMID:36949865 | PMC:PMC10025951 | DOI:10.1016/j.ejvsvf.2023.02.003

Can J Gastroenterol Hepatol. 2023 Mar 11;2023:2877350. doi: 10.1155/2023/2877350. eCollection 2023.

ABSTRACT

BACKGROUND: Ataxia-telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition, and altered body composition. Liver diseases with steatosis, fibrosis, and hepatocellular carcinoma are frequent findings in older patients but sensitive noninvasive diagnostic tools are lacking.

OBJECTIVES: To determine the sensitivity of transient elastography (TE) as a screening tool for early hepatic tissue changes and serum biomarkers for liver disease.

METHODS: Thirty-one A-T patients aged 2 to 25 years were examined prospectively from 2016-2018 by TE. In addition, we evaluated the diagnostic performance of liver biomarkers for steatosis and necroinflammatory activity (SteatoTest and ActiTest, Biopredictive, Paris) compared to TE. For calculation and comparison, patients were divided into two groups (<12, >12 years of age).

RESULTS: TE revealed steatosis in 2/21 (10%) younger patients compared to 9/10 (90%) older patients. Fibrosis was present in 3/10 (30%) older patients as assessed by TE. We found a significant correlation of steatosis with SteatoTest, alpha-fetoprotein (AFP), HbA1c, and triglycerides. Liver stiffness correlated significantly with SteatoTest, ActiTest, HbA1c, and triglycerides.

CONCLUSION: Liver disease is a common finding in older A-T patients. TE is an objective measure to detect early stages of steatosis and fibrosis. SteatoTest and ActiTest are a good diagnostic assessment for steatosis and necroinflammatory activity in patients with A-T and confirmed the TE results.

PMID:36941982 | PMC:PMC10024628 | DOI:10.1155/2023/2877350

J Coll Physicians Surg Pak. 2023 Mar;33(3):341-345. doi: 10.29271/jcpsp.2023.03.341.

ABSTRACT

OBJECTIVE: To determine the outcomes of allogeneic HSCT in children with primary immune system disorders (PID).

STUDY DESIGN: Descriptive Cross-sectional study. Place and Duration of the Study: Armed Forces bone marrow transplant centre / National Institute of Bone Marrow Transplant (AFBMTC / NIBMT), Rawalpindi, Pakistan, from October 2012 to December 2021.

METHODOLOGY: Data of all cases undergoing HSCT for immune system disorders were analysed for variables affecting outcome and overall survival in the first 180 days after allogeneic HSCT. All patients presenting to AFBMTC / NIBMT with PID, age <12 years. Patients with organ dysfunction secondary to repeated infections were excluded from the study. Data of all patients and their donors undergoing HSCT for immune system disorders were analysed for variables affecting outcome and overall survival in the first 180 days after allogeneic bone marrow transplant. Neutrophil engraftment was defined as absolute neutrophil count ≥0.5 × 109/L for 3 consecutive days, while platelet engraftment as platelet count ≥20 × 109/L without platelet transfusion for one week. Overall survival (OS) was taken as time from the date of HSCT till day + 180 post-transplant.

RESULTS: A total of 42children including 29 boys and 13 girls underwent HSCT for PID. The mean age was 2.1±2.8 years. Underlying diagnosis was haemophagocytic lymphohistiocytosis (HLH), severe immune deficiency (SCID), leukocyte adhesion defect (LAD), X-linked agammaglobulinemia, chronic granulomatous disease (CGD) and Job’s syndrome in 18 (42.9%), 16 (38.1%), 3(7.1%), 2 (4.8%), 2 (4.8%) and 1 (2.4%) patients respectively. Thirty-one (73.8%) children had fully HLA-matched donors while 11 (26.2%) had haplo-matched donors. Major immediate post-transplant complications were febrile neutropenia, mucositis and SOS/VOD in 31 (73.8%), 9 (21.4%) and 4 (10.0%) cases, respectively. Eight (19.0%) had CMV reactivation, acute GVHD was seen in 17 (40.4%) cases, while 1 (2.3%) case had chronic GVHD. Twelve (28.6%) patients died, out of which 5 had graft failure, 3 had VOD, 2 had pneumonia, 1 had severe GVHD, and 1 died due to seizures. Overall survival (OS) in this study was 71.4% with survival reaching up to 80.6% in fully matched HSCT.

CONCLUSION: HLH and SCID were the commonest immune disorders requiring HSCT. Graft failure leading to neutropenic sepsis was the commonest cause of mortality. OS was better in fully matched HSCT as compared to haplo-identical HSCT.

KEY WORDS: Immune deficiency, Severe combined immunodeficiency, Haematopoietic stem cell transplantation.

PMID:36945167 | DOI:10.29271/jcpsp.2023.03.341