Research

J Allergy Clin Immunol. 2023 May 18:S0091-6749(23)00606-1. doi: 10.1016/j.jaci.2023.05.006. Online ahead of print.

ABSTRACT

BACKGROUND: – Primary immunodeficiencies (PID) are a heterogeneous group of rare inborn immunity defects. As management has greatly improved, morbi-mortality is reduced in this population, while our knowledge on pregnancy unfolding and outcome remains scarce.

OBJECTIVE: We conducted a retrospective monocentric study to study pregnancy outcomes in women with PID.

METHODS: The study cohort consisted of women over 18 included in the national registry for PID (CEREDIH), living in the greater Paris area, reporting ≥1 pregnancy. Data were collected through a standardized questionnaire and medical records. We analyzed PID features, pregnancy course and outcome, and neonatal features (NCT04581460).

RESULTS: We studied 93 women with PID (27 combined immunodeficiencies, 51 predominantly antibody deficiencies, and 15 innate immunodeficiencies) and their 222 pregnancies (67, 119 and 36 in each ID group respectively). One hundred and fifty four out of 222 (69%) pregnancies led to 157 live births including 4 severe preterm births (3%), in the range of pregnancy outcome in French general population. In a multivariate model, poor obstetrical outcome (fetal loss or pregnancy termination) was associated with history of severe infection (adjusted Odds Ratio of 0.28, [95% confidence interval 0.11-0.67], p=0.005). Only 59% pregnancies were led with optimal anti-infective prophylaxis; severe infections were reported in only 2 pregnancies (1%). One infant died during the neonatal period.

CONCLUSION: Pregnancy is achievable in women with a wide group of PID. Prematurity is increased and history of severe infection is associated with significant increase of fetal loss/pregnancy termination. Adjustment of care during pregnancy needs to be better delivered.

PMID:37210041 | DOI:10.1016/j.jaci.2023.05.006

J Crit Care. 2023 May 17;77:154300. doi: 10.1016/j.jcrc.2023.154300. Online ahead of print.

ABSTRACT

PURPOSE: Infectious encephalitis (IE) is a severe disease which requires intensive care unit (ICU) admission in up to 50% of cases. We aimed to describe characteristics, management and outcomes of IE patients who required ICU admission.

MATERIALS AND METHODS: Ancillary study focusing on patients with ICU admission within the ENCEIF cohort, a French prospective observational multicentre study. The primary criteria for outcome was the functional status at hospital discharge, categorized using the Glasgow outcome scale (GOS). Logistic regression model was used to identify risk factors for poor outcome, defined as a GOS ≤ 3.

RESULTS: We enrolled 198 ICU patients with IE. HSV was the primary cause (n = 72, 36% of all IE, 53% of IE with microbiological documentation). Fifty-two patients (26%) had poor outcome at hospital discharge, including 22 deaths (11%). Immunodeficiency, supratentorial focal signs on admission, lower cerebrospinal fluid (CSF) white cells count (<75/mm3), abnormal brain imaging, and time from symptoms onset to acyclovir start >2 days were independent predictors of poor outcome.

CONCLUSION: HSV is the primary cause of IE requiring ICU admission. IE patients admitted in ICU have a poor prognosis with 11% of in-hospital mortality and 15% of severe disabilities in survivors at discharge.

PMID:37207520 | DOI:10.1016/j.jcrc.2023.154300

Paediatr Child Health. 2023 Mar 28;28(3):145-150. doi: 10.1093/pch/pxac076. eCollection 2023 Jun.

ABSTRACT

Cow’s milk allergy (CMA) is one of the most common food allergies in the first years of life, with worldwide prevalence estimated to range from 2% to 5%. While the majority of children with CMA will eventually develop tolerance to cow’s milk proteins (it is estimated that >75% of children with CMA develop tolerance to cow’s milk proteins by the age of 3 years, and >90% develop tolerance by the age of 6 years), the selection of an appropriate cow’s milk (CM) alternative for those with CMA is vital to ensure adequate growth and development during childhood. The increasing number of CM alternative products on the commercial market with markedly different nutritional content and micronutrient fortification adds a layer of complexity that can be challenging for both families and clinicians to navigate. This article aims to provide guidance and clarity to Canadian paediatricians and primary care clinicians on recommending the most appropriate, safe, and nutritionally optimal CM alternatives for individuals with CMA, and beyond.

PMID:37205135 | PMC:PMC10186100 | DOI:10.1093/pch/pxac076

JPGN Rep. 2021 Jul 12;2(3):e102. doi: 10.1097/PG9.0000000000000102. eCollection 2021 Aug.

ABSTRACT

X-linked lymphoproliferative syndrome type 2 (XLP2) is a rare genetic primary immunodeficiency disease caused by mutations in the XIAP gene that lead to deficiency of the X-linked inhibitor of apoptosis protein. XLP2 is characterized by dysregulated immune responses and can result in an inflammatory bowel disease (IBD)-like phenotype, a form of monogenic IBD. Patients with XLP2 often succumb to fulminant hemophagocytic lymphohistiocytosis or Epstein-Barr virus infections. Hematopoietic stem cell transplantation (HSCT) is currently the only definitive treatment for XLP2. We report an adolescent with a delayed diagnosis of XLP2 in the setting of severe Crohn’s disease diagnosed at age 9 years and recurrent skin infections. He is under evaluation for HSCT. Gastroenterologists must recognize monogenic IBD in patients of all ages with severe disease and signs of an underlying primary immunodeficiency disease. Patients with suspected monogenic IBD should undergo immunologic and genetic analysis at diagnosis to initiate potentially life-saving treatment.

PMID:37205951 | PMC:PMC10191492 | DOI:10.1097/PG9.0000000000000102

J Clin Immunol. 2023 May 19. doi: 10.1007/s10875-023-01503-w. Online ahead of print.

ABSTRACT

PURPOSE: Diarrhea lasting longer than 14 days which fails to respond to conventional management is defined as severe and protracted diarrhea and might overlap with inflammatory bowel disease (IBD).

METHODS: The prevalence, associated pathogens, and prognosis of severe and protracted diarrhea without IBD (SD) and with monogenetic IBD (mono-IBD) in primary immunodeficiency patients (PID) were investigated in Taiwan.

RESULTS: A total of 301 patients were enrolled between 2003 and 2022, with predominantly pediatric-onset PID. Of these, 24 PID patients developed the SD phenotype before prophylactic treatment, including Btk (six), IL2RG (four), WASP, CD40L, gp91 (three each), gp47, RAG1 (one each), CVID (two), and SCID (one) without identified mutations. The most detectable pathogens were pseudomonas and salmonella (six each), and all patients improved after approximately 2 weeks of antibiotic and/or IVIG treatments. Six (25.0%) mortalities without HSCT implementation were due to respiratory failure from interstitial pneumonia (3 SCID and 1 CGD), intracranial hemorrhage (WAS), and lymphoma (HIGM). In the mono-IBD group, seventeen patients with mutant TTC7A (2), FOXP3 (2), NEMO (2), XIAP (2), LRBA (1), TTC37 (3), IL10RA (1), STAT1 (1), ZAP70 (1), PIK3CD (1), and PIK3R1 (1) genes failed to respond to aggressive treatments. Nine mono-IBD patients with TTC7A (2), FOXP3 (2), NEMO (2), XIAP (2), and LRBA (1) mutations were fatal in the absence of HSCT. The mono-IBD group had a significantly earlier age of diarrhea onset (1.7 vs 33.3 months, p = 0.0056), a longer TPN duration (34.2 vs 7.0 months, p < 0.0001), a shorter follow-up period (41.6 vs 132.6 months, p = 0.007), and a higher mortality rate (58.9 vs 25.0%, p = 0.012) compared with the SD group.

CONCLUSION: When compared to those with the SD phenotype, the mono-IBD patients had significant early-onset and poor responses to empiric antibiotics, IVIG, and steroids. Anti-inflammatory biologics and suitable HSCT still have the potential to control or even cure the mono-IBD phenotype.

PMID:37202577 | DOI:10.1007/s10875-023-01503-w

Rev Med Inst Mex Seguro Soc. 2023 Mar 1;61(2):189-195.

ABSTRACT

The autoimmune diseases include many in which the immune system is directed against the host, leading to life-threatening destruction of organs. The origin of autoimmune disorders can be multifactorial and, there are no specific therapy for these diseases. Primary immunodeficiencies are a group of immune disorders that affect different components of the innate and adaptive responses. Interestingly, patients with primary immunodeficiencies have an increased susceptibility to infectious diseases and non-infectious complications including allergies, malignancies, and autoimmune diseases. The molecular mechanism for development of autoimmunity in immunodeficiencies is unclear. The study of the complex immune regulatory and signaling mechanisms is revealing the relationships between primary immunodeficiency syndromes and autoimmune diseases. Newly, it has been demonstrated that a deficient maturation of immune cells; the deficiency of proteins important for T and B lymphocyte function and impaired signally pathways that include key molecules in regulation and activation of immune cells are associated with the development of autoimmunity in patients with primary immunodeficiencies. The aim of the present work is to review the evidence available to date regarding the cellular and molecular mechanisms involved in the development of autoimmunity in patients with primary immunodeficiencies.

PMID:37200522

Inflammopharmacology. 2023 May 17. doi: 10.1007/s10787-023-01222-z. Online ahead of print.

ABSTRACT

Sjögren’s syndrome (SS) is characterised as keratoconjunctivitis sicca (dry eyes), xerostomia (dry mouth) commonly associated with salivary gland enlargement, and is referred to as Primary Sjögren’s syndrome. It is known as Secondary Sjögren’s syndrome when it occurs in patients, with connective tissue disease, such as rheumatoid arthritis, systemic lupus erythematosus, polyarthritis nodosa, polymyositis, and systemic sclerosis. SS has also been associated with chronic graft-versus-host disease after allogeneic bone marrow transplantation, human immunodeficiency syndrome (AIDS), hepatitis C infection (HCV), chronic biliary cirrhosis, neoplastic and myeloplastic syndromes, fibromyalgia, and chronic fatigue syndrome.

PMID:37195497 | DOI:10.1007/s10787-023-01222-z

Clin Case Rep. 2023 May 12;11(5):e7341. doi: 10.1002/ccr3.7341. eCollection 2023 May.

ABSTRACT

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder that is characterized by deficiencies in the phagocytes capacity to eliminate ingested microorganisms, which frequently causes bacterial and fungal infections. The extensive involvement of the lungs, ribs, and vertebrae that is complicated by multiple abscesses from aspergillosis is rare. in this study, we report a 13-year-old boy with CGD who experienced concurrent pneumonia, rib osteomyelitis, spondylodiscitis, paravertebral, and epidural abscesses as a result of Aspergillus flavus infection with associated computed tomography scan and magnetic resonance imaging findings. Patients with CGD are susceptible to Aspergillus infection. Correct diagnosis based on clinical and paraclinical findings as well as choosing the best treatment regimen is essential for achieving a favorable outcome.

PMID:37192846 | PMC:PMC10182263 | DOI:10.1002/ccr3.7341

Biomedicines. 2023 Mar 28;11(4):1042. doi: 10.3390/biomedicines11041042.

ABSTRACT

Patients with antibody deficiency disorders, such as primary immunodeficiency (PID) or secondary immunodeficiency (SID) to B-cell lymphoproliferative disorder (B-CLPD), are two groups vulnerable to developing the severe or chronic form of coronavirus disease caused by SARS-CoV-2 (COVID-19). The data on adaptive immune responses against SARS-CoV-2 are well described in healthy donors, but still limited in patients with antibody deficiency of a different cause. Herein, we analyzed spike-specific IFN-γ and anti-spike IgG antibody responses at 3 to 6 months after exposure to SARS-CoV-2 derived from vaccination and/or infection in two cohorts of immunodeficient patients (PID vs. SID) compared to healthy controls (HCs). Pre-vaccine anti-SARS-CoV-2 cellular responses before vaccine administration were measured in 10 PID patients. Baseline cellular responses were detectable in 4 out of 10 PID patients who had COVID-19 prior to vaccination, perceiving an increase in cellular responses after two-dose vaccination (p < 0.001). Adequate specific cellular responses were observed in 18 out of 20 (90%) PID patients, in 14 out of 20 (70%) SID patients and in 74 out of 81 (96%) HCs after vaccination (and natural infection in some cases). Specific IFN-γ response was significantly higher in HC with respect to PID (1908.5 mUI/mL vs. 1694.1 mUI/mL; p = 0.005). Whereas all SID and HC patients mounted a specific humoral immune response, only 80% of PID patients showed positive anti-SARS-CoV-2 IgG. The titer of anti-SARS-CoV-2 IgG was significantly lower in SID compared with HC patients (p = 0.040), without significant differences between PID and HC patients (p = 0.123) and between PID and SID patients (p =0.683). High proportions of PID and SID patients showed adequate specific cellular responses to receptor binding domain (RBD) neoantigen, with a divergence between the two arms of the adaptive immune response in PID and SID patients. We also focused on the correlation of protection of positive SARS-CoV-2 cellular response to omicron exposure: 27 out of 81 (33.3%) HCs referred COVID-19 detected by PCR or antigen test, 24 with a mild course, 1 with moderate symptoms and the remaining 2 with bilateral pneumonia that were treated in an outpatient basis. Our results might support the relevance of these immunological studies to determine the correlation of protection with severe disease and for deciding the need for additional boosters on a personalized basis. Follow-up studies are required to evaluate the duration and variability in the immune response to COVID-19 vaccination or infection.

PMID:37189660 | DOI:10.3390/biomedicines11041042

Urol Case Rep. 2023 May 1;48:102409. doi: 10.1016/j.eucr.2023.102409. eCollection 2023 May.

ABSTRACT

Chronic Granulomatous Disease is a primary immunodeficiency syndrome caused by a phagocytic defect, characterized by recurrent, life-threatening bacterial and fungal infections and an excessive inflammatory response. We present the case of a boy with disease’s symptoms mainly from the genitourinary tract. We describe diagnostic difficulties and atypical cystoscopic images, which showed bright morphotic elements of unclear etiology moving in the vessels of the bladder mucosa. These lesions were retrospectively interpreted as clusters of white blood cells (granulomas). Due to the lack of description of a similar phenomenon in the literature, we would like to make the recorded endoscopic images available.

PMID:37187765 | PMC:PMC10176158 | DOI:10.1016/j.eucr.2023.102409