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Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2022To evaluate the clinical effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with hyper-IgM syndrome (HIGM).
OBJECTIVES
To evaluate the clinical effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with hyper-IgM syndrome (HIGM).
METHODS
A retrospective analysis was performed on the medical data of 17 children with HIGM who received allo-HSCT. The Kaplan Meier method was used for the survival analysis of the children with HIGM after allo-HSCT.
RESULTS
After allo-HSCT, 16 children were diagnosed with sepsis; 14 tested positive for virus within 100 days after allo-HSCT, among whom 11 were positive for Epstein-Barr virus, 7 were positive for cytomegalovirus, and 2 were positive for JC virus; 9 children were found to have invasive fungal disease. There were 6 children with acute graft-versus-host disease and 3 children with chronic graft-versus-host disease. The median follow-up time was about 2 years, and 3 children died in the early stage after allo-HSCT. The children had an overall survival (OS) rate of 82.35%, an event-free survival (EFS) rate of 70.59%, and a disease-free survival (DFS) rate of 76.47%. The univariate analysis showed that the children receiving HLA-matched allo-HSCT had a significantly higher EFS rate than those receiving HLA-mismatched allo-HSCT (=0.019) and that the children receiving HLA-matched unrelated allo-HSCT had significantly higher OS, EFS, and DFS rates than those receiving HLA-mismatched unrelated allo-HSCT (<0.05). Compared with the children with fungal infection after allo-HSCT, the children without fungal infection had significantly higher EFS rate (=0.02) and DFS rate (=0.04).
CONCLUSIONS
Allo-HSCT is an effective treatment method for children with HIGM. HLA-matched allo-HSCT and active prevention and treatment of fungal infection and opportunistic infection may help to improve the prognosis of such children.
Topics: Child; Epstein-Barr Virus Infections; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Humans; Hyper-IgM Immunodeficiency Syndrome; Retrospective Studies
PubMed: 35762429
DOI: 10.7499/j.issn.1008-8830.2112098 -
JPMA. the Journal of the Pakistan... May 2022Berardinelli Seip Congenital Lipodystrophy (BSCL) or Congenital Generalized Lipodystrophy (CGL) is one of the four subgroups of lipodystrophy syndrome which is...
Berardinelli Seip Congenital Lipodystrophy (BSCL) or Congenital Generalized Lipodystrophy (CGL) is one of the four subgroups of lipodystrophy syndrome which is characterized by varying degrees of loss of adipose mass in the body. It is an extremely rare autosomal recessive disorder and commonly reported clinical presentations include muscular hypertrophy, gigantism, hepatomegaly, impaired glucose tolerance, acanthosis nigricans, hypertriglyceridaemia, cardiomyopathy, intellectual impairment, bone cysts and phlebomegaly. We present a case of a 4.5 years old male child born to consanguineous parents, presented with pneumonia. There was history of recurrent diarrhea and chest infection in the past. He had acromegaly like features, hirsutism, firm hepatomegaly, a well defined bone cyst in proximal right femur, pancytopenias with normal bone marrow biopsy report, hypertriglyceridemia and selective IgA deficiency. This is the first case of BSCL, reported in Pakistan with a bone cyst and IgA deficiency. Such patients need to be identified and monitored for complications like diabetes mellitus and hypertrophic cardiomyopathy.
Topics: Bone Cysts; Child, Preschool; Hepatomegaly; Humans; IgA Deficiency; Lipodystrophy; Lipodystrophy, Congenital Generalized; Male
PubMed: 35713067
DOI: 10.47391/JPMA.3182 -
Frontiers in Genome Editing 2022X-linked lymphoproliferative disease is a rare inherited immune disorder, caused by mutations or deletions in the gene that encodes an intracellular adapter protein SAP...
X-linked lymphoproliferative disease is a rare inherited immune disorder, caused by mutations or deletions in the gene that encodes an intracellular adapter protein SAP (Slam-associated protein). SAP is essential for mediating several key immune processes and the immune system - T cells in particular - are dysregulated in its absence. Patients present with a spectrum of clinical manifestations, including haemophagocytic lymphohistiocytosis (HLH), dysgammaglobulinemia, lymphoma and autoimmunity. Treatment options are limited, and patients rarely survive to adulthood without an allogeneic haematopoietic stem cell transplant (HSCT). However, this procedure can have poor outcomes in the mismatched donor setting or in the presence of active HLH, leaving an unmet clinical need. Autologous haematopoeitic stem cell or T cell therapy may offer alternative treatment options, removing the need to find a suitable donor for HSCT and any risk of alloreactivity. SAP has a tightly controlled expression profile that a conventional lentiviral gene delivery platform may not be able to fully replicate. A gene editing approach could preserve more of the endogenous regulatory elements that govern SAP expression, potentially providing a more optimum therapy. Here, we assessed the ability of TALEN, CRISPR-Cas9 and CRISPR-Cas12a nucleases to drive targeted insertion of cDNA at the first exon of the locus using an adeno-associated virus serotype 6 (AAV6)-based vector containing the donor template. All nuclease platforms were capable of high efficiency gene editing, which was optimised using a serum-free AAV6 transduction protocol. We show that T cells from XLP patients corrected by gene editing tools have restored physiological levels of gene expression and restore SAP-dependent immune functions, indicating a new therapeutic opportunity for XLP patients.
PubMed: 35677600
DOI: 10.3389/fgeed.2022.828489 -
Respiratory Research May 2022Immunoglobulin G (IgG) deficiency increases the risk of acute exacerbations and mortality in chronic obstructive pulmonary disease (COPD). However, the impact of IgG...
BACKGROUND
Immunoglobulin G (IgG) deficiency increases the risk of acute exacerbations and mortality in chronic obstructive pulmonary disease (COPD). However, the impact of IgG subclass deficiency on mortality in COPD is unknown. Here, we determined which IgG subclass, if any, is associated with increased risk of mortality in COPD.
METHODS
We measured serum IgG subclass concentrations of 489 hospitalized patients with COPD who were enrolled in the Rapid Transition Program (clinicaltrials.gov identifier NCT02050022). To evaluate the impact of IgG subclass deficiency on 1-year mortality, Cox proportional hazards regression analyses were performed with adjustments for potential confounders.
RESULTS
Deficiencies in IgG1, IgG2, IgG3, and IgG4 were present in 1.8%, 12.1%, 4.3%, and 11.2% of patients, respectively. One-year mortality was 56% in patients with IgG1 deficiency, 27% in IgG2 deficiency, 24% in IgG3 deficiency, and 31% in IgG4 deficiency. Cox proportional modeling showed that IgG1 and IgG4 deficiencies increased the 1-year mortality risk with an adjusted hazard ratio of 3.92 (95% confidence interval [CI] = 1.55-9.87) and 1.74 (95% CI = 1.02-2.98), respectively. Neither IgG2 nor IgG3 deficiency significantly increased 1-year mortality. Two or more IgG subclass deficiencies were observed in 5.3%. Patients with 2 or more IgG subclass deficiencies had a higher 1-year mortality than those without any deficiencies (46.2% vs. 19.7%, p < 0.001), with an adjusted hazard ratio of 2.22 (95% CI = 1.18-4.17).
CONCLUSIONS
IgG1 and IgG4 deficiency was observed in 1.8% and 11.2% of hospitalized patients with COPD, respectively, and these deficiencies were associated with a significantly increased risk of 1-year mortality.
Topics: Humans; IgG Deficiency; Immunoglobulin G; Immunologic Deficiency Syndromes; Pulmonary Disease, Chronic Obstructive
PubMed: 35641962
DOI: 10.1186/s12931-022-02052-3 -
Frontiers in Immunology 2022X-linked hyper-IgM (XHIGM) syndrome is caused by mutations of the CD40LG gene, encoding the CD40L protein. The clinical presentation is characterized by early-onset...
X-linked hyper-IgM (XHIGM) syndrome is caused by mutations of the CD40LG gene, encoding the CD40L protein. The clinical presentation is characterized by early-onset infections, with profound hypogammaglobulinemia and often elevated IgM, susceptibility to opportunistic infections, such as pneumonia, biliary tract disease due to , and malignancy. We report a 41-year-old male presenting with recurrent leishmaniasis, hypogammaglobulinemia, and myopathy. Whole-exome sequencing (WES) identified a missense variant in the CD40LG gene (c.107T>A, p.M36K), involving the transmembrane domain of the protein and a missense variant in the carnitine palmitoyl-transferase II (CPT2; c.593C>G; p.S198C) gene, leading to the diagnosis of hypomorphic XHIGM and CPT2 deficiency stress-induced myopathy. A review of all the previously reported cases of XHIGM with variants in the transmembrane domain showcased that these patients could present with atypical clinical features. Variants in the transmembrane domain of CD40LG act as hypomorphic generating a protein with a lower surface expression. Unlike large deletions or extracellular domain variants, they do not abolish the interaction with CD40, therefore preserving some biological activity.
Topics: Adult; Agammaglobulinemia; CD40 Ligand; Cryptosporidiosis; Cryptosporidium; Humans; Hyper-IgM Immunodeficiency Syndrome; Hyper-IgM Immunodeficiency Syndrome, Type 1; Immunoglobulin M; Leishmaniasis; Male
PubMed: 35572607
DOI: 10.3389/fimmu.2022.840767 -
Romanian Journal of Ophthalmology 2022We present the case of a 35-year-old female patient, pregnant in her third trimester, with no ophthalmologic history of interest and a medical history of IgA deficiency...
We present the case of a 35-year-old female patient, pregnant in her third trimester, with no ophthalmologic history of interest and a medical history of IgA deficiency syndrome with bronchiectasis as the only symptomatology, who came to another center with clinical symptoms of ocular discomfort. She was initially diagnosed with anterior uveitis and treated with topical and periocular corticosteroids. Edema and palpebral erythema appeared a few days later and she was diagnosed with idiopathic orbital inflammation and was treated with intravenous (I.V.) corticosteroids, which led to the appearance of a purulent palpebral and subconjunctival collection with a diagnosis of orbital cellulitis. At this time, she came to our center, where ultrasound and magnetic resonance imaging (MRI) showed intraocular and scleral destructuring with scleral perforation. The subconjunctival abscess was drained, being positive for , and sputum culture was positive for , so she was diagnosed with endogenous endophthalmitis due to transient bacteremia in the context of IgA deficiency syndrome and treated with antibiotherapy. Despite the improvement of the infectious clinic, the persistence of positive cultures for and the evolution to phthisis bulbi at 2 months led to definitive treatment with evisceration. To our knowledge, this is the first reported case of endogenous endophthalmitis associated with IgA deficiency and the first reported case of endogenous bacterial endophthalmitis caused by during pregnancy.
Topics: Adult; Anti-Bacterial Agents; Endophthalmitis; Eye Infections, Bacterial; Female; Humans; IgA Deficiency; Pregnancy; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 35531454
DOI: 10.22336/rjo.2022.19 -
Frontiers in Immunology 2022Here we describe a novel mutation in the gene encoding IKAROS, as the cause of common variable immunodeficiency (CVID). The identification of the same defect in the...
Here we describe a novel mutation in the gene encoding IKAROS, as the cause of common variable immunodeficiency (CVID). The identification of the same defect in the gene with manifestations of asymptomatic selective IgA deficiency and chronic ITP in the father and her younger brother, respectively, demonstrates the large variability of this genetic defect in one single family, while living in the same environment with a relatively similar genetic background. As discussed, clinical penetrance of the molecular defects identified by mutations in and other common gene defects in CVID in familial immune-related abnormalities makes genetic testing a necessary step for diagnosis, management, and counseling, as part of the routine immunological workup.
Topics: Common Variable Immunodeficiency; Female; Humans; IgA Deficiency; Male; Mutation
PubMed: 35479066
DOI: 10.3389/fimmu.2022.865838 -
Anales de Pediatria Sep 2022(1) To describe the prevalence of IgA deficiency (IgAD), uveitis, coeliac disease (CD) and thyroid disorders in a multicentric cohort of patients diagnosed with JIA and,...
OBJECTIVES
(1) To describe the prevalence of IgA deficiency (IgAD), uveitis, coeliac disease (CD) and thyroid disorders in a multicentric cohort of patients diagnosed with JIA and, (2) to evaluate whether patients with JIA and IgAD present other autoimmune diseases more frequently than patients with normal serum levels of IgA.
METHODS
Retrospective chart review of a cohort of patients diagnosed with JIA followed at the paediatric rheumatology units of two hospitals in Madrid, Spain.
RESULTS
A total of 193 patients were included. Of them, 123 were females (64%). Median age at disease onset was 5.6 years (IQR 2.5-9.7) and the median time of follow-up was 5.1 years (IQR 2.2-8.1). The three most common ILAR categories were oligoarticular (53%), polyarticular RF negative (20%) and enthesitis related arthritis (10%). Serum IgA levels were available in 172/193 (89%); 25/172 (15%) had selective (<7mg/dl, n=8) or partial (7-69mg/dl, n=17) IgAD. All the patients had periodic eye exams. Eighteen children (9%) had anterior uveitis, 15/18 chronic and 3/18 acute. Serum anti transglutaminase IgA, or IgG in IgAD were obtained in 135/193 (70%). Four children (3%) were diagnosed with CD either by intestinal biopsy (n=3) or by the combination of characteristic clinical, serological and genetic features (n=1); two of them had IgAD (p=0.12; OR=6.4; 95% CI 0.9-47.6). Only 1/153 (0.7%) patient had hyperthyrotropinemia with positive anti-thyroid antibodies and required replacement therapy.
CONCLUSION
Patients with JIA frequently present autoimmune comorbidities. IgAD does not seem to increase their prevalence, with the possible exception of CD.
Topics: Arthritis, Juvenile; Celiac Disease; Child; Child, Preschool; Female; Humans; IgA Deficiency; Immunoglobulin A; Male; Retrospective Studies; Transglutaminases
PubMed: 35459637
DOI: 10.1016/j.anpede.2022.03.004 -
Archivum Immunologiae Et Therapiae... Apr 2022Hydroxychloroquine (HCQ) therapy decreased immunoglobulin (Ig) levels in patients with Sjögren syndrome (SS) and rheumatoid arthritis (RA) in previous studies. We found...
Hydroxychloroquine Therapy and Serum Immunoglobulin Levels in Women with IgG Subclass Deficiency and Systemic Lupus Erythematosus, Sjögren Syndrome, and Rheumatoid Arthritis: A Retrospective Study.
Hydroxychloroquine (HCQ) therapy decreased immunoglobulin (Ig) levels in patients with Sjögren syndrome (SS) and rheumatoid arthritis (RA) in previous studies. We found no report of Ig levels of women with IgG subclass deficiency (IgGSD) and systemic lupus erythematosus (SLE), SS, or RA treated with HCQ. We retrospectively evaluated IgG, IgG subclass, IgA, and IgM levels and other characteristics of women at IgGSD diagnosis who did and did not take HCQ for SLE, SS, or RA. There were 132 women (48 subnormal IgG1 only, 49 combined subnormal IgG1/IgG3, and 35 subnormal IgG3 only). Mean age was 49 ± 13 years. Twenty-two women with SLE, SS, RA, or combination thereof reported HCQ ≥ 200 mg/day ≥ 6 months. In each IgGSD subtype, median Ig levels of women who took HCQ were not significantly lower than those of women who did not take HCQ. Women with combined subnormal IgG1/IgG3 who took HCQ had greater median IgG2 than women who did not take HCQ (4.89 g/L (range 4.43, 4.94) vs. 2.57 g/L (1.21, 6.44), respectively; p = 0.0123). Regressions on IgG1, IgG2, and IgG3 revealed positive associations with HCQ therapy (p = 0.0043, 0.0037, and 0.0139, respectively). There were no significant Ig associations with age, SLE, SS, or RA as independent variables. HCQ therapy of SLE, SS, or RA in women with IgGSD was not associated with significantly lower IgG, IgG subclass, IgA, or IgM levels. IgG1, IgG2, and IgG3 were positively associated with HCQ therapy, after adjustment for other variables.
Topics: Adult; Arthritis, Rheumatoid; Female; Humans; Hydroxychloroquine; IgG Deficiency; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Lupus Erythematosus, Systemic; Middle Aged; Retrospective Studies; Sjogren's Syndrome
PubMed: 35403913
DOI: 10.1007/s00005-022-00652-x -
BMC Pediatrics Apr 2022Hyper IgM syndromes (HIGMS) are a group of rare primary immunodeficiency disorders. There are limited reports about HIGMS combined with severe eosinophilia. (Review)
Review
BACKGROUND
Hyper IgM syndromes (HIGMS) are a group of rare primary immunodeficiency disorders. There are limited reports about HIGMS combined with severe eosinophilia.
CASE PRESENTATION
In this report, we described a 2-year-old boy with chronic cough and symptoms of hypoxia. Lung computed tomography (CT) scan showed that diffuse ground-glass changes and eosinophils in peripheral blood increased significantly. Subsequent tests revealed a notable decrease in serum IgG and IgA. The lymphocyte subgroup classification was basically normal. Pneumocystis jirovecii were detected from the bronchoalveolar lavage fluid (BALF) of the patient by metagenomic next-generation sequencing (mNGS). After treatments of caspofungin combined with sulfamethoxazole, intravenous immunoglobulin (IVIG) replacement and anti-inflammatory steroid, the clinical symptoms and pulmonary imaging noticeably improved. The absolute eosinophil count (AEC) also returned to normal range. X-linked hyper IgM syndrome was confirmed by gene test. Two months after the diagnosis, the patient underwent allogeneic stem cell transplantation (HSCT) and has recovered well.
CONCLUSIONS
Children with HIGMS are prone to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). Diffuse interstitial lung disease and hypoglobulinemia in a young child predict the diagnosis of a primary immunodeficiency (PID). mNGS has obvious advantages for obtaining etiological diagnosis of children with PIDs. Severe eosinophilia is rarely reported in this kind of PIDs. Considering literature review and the corresponding reaction to steroid, we proposed that eosinophilia in HIGMS might be related to infections. Steroid therapy can quickly relieve eosinophilia but is easy to rebound if the reduction is too fast. Once the diagnosis of HIGMS is confirmed, the earlier the HSCT, the better the prognosis.
Topics: Anti-Inflammatory Agents; Child; Child, Preschool; Eosinophilia; Hematopoietic Stem Cell Transplantation; Humans; Hyper-IgM Immunodeficiency Syndrome; Hyper-IgM Immunodeficiency Syndrome, Type 1; Male
PubMed: 35379217
DOI: 10.1186/s12887-022-03251-z