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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 -
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 -
The Journal of Allergy and Clinical... Apr 2019Commensals induce local IgA responses essential to the induction of tolerance to gut microbiota, but it remains unclear whether antimicrobiota responses remain confined...
BACKGROUND
Commensals induce local IgA responses essential to the induction of tolerance to gut microbiota, but it remains unclear whether antimicrobiota responses remain confined to the gut.
OBJECTIVE
The aim of this study was to investigate systemic and intestinal responses against the whole microbiota under homeostatic conditions and in the absence of IgA.
METHODS
We analyzed blood and feces from healthy donors, patients with selective IgA deficiency (SIgAd), and patients with common variable immunodeficiency (CVID). Immunoglobulin-coated bacterial repertoires were analyzed by using combined bacterial fluorescence-activated cell sorting and 16S rRNA sequencing. Bacterial lysates were probed by using Western blot analysis with healthy donor sera.
RESULTS
Although absent from the healthy gut, serum antimicrobiota IgG are present in healthy subjects and increased in patients with SIgAd. IgG converges with nonoverlapping secretory IgA specificities to target the same bacteria. Each individual subject targets a diverse microbiota repertoire with a proportion that correlates inversely with systemic inflammation. Finally, intravenous immunoglobulin preparations target CVID gut microbiota much less efficiently than healthy microbiota.
CONCLUSION
Secretory IgA and systemic IgG converge to target gut microbiota at the cellular level. SIgAd-associated inflammation is inversely correlated with systemic anticommensal IgG responses, which might serve as a second line of defense. We speculate that patients with SIgAd could benefit from oral IgA supplementation. Our data also suggest that intravenous immunoglobulin preparations can be supplemented with IgG from IgA-deficient patient pools to offer better protection against gut bacterial translocations in patients with CVID.
Topics: Antibodies, Bacterial; Common Variable Immunodeficiency; Feces; Gastrointestinal Microbiome; Humans; IgA Deficiency; Immunoglobulin A, Secretory; Immunoglobulin G
PubMed: 30554723
DOI: 10.1016/j.jaci.2018.09.036 -
EMBO Molecular Medicine Mar 2021Precise correction of the CD40LG gene in T cells and hematopoietic stem/progenitor cells (HSPC) holds promise for treating X-linked hyper-IgM Syndrome (HIGM1), but its...
Precise correction of the CD40LG gene in T cells and hematopoietic stem/progenitor cells (HSPC) holds promise for treating X-linked hyper-IgM Syndrome (HIGM1), but its actual therapeutic potential remains elusive. Here, we developed a one-size-fits-all editing strategy for effective T-cell correction, selection, and depletion and investigated the therapeutic potential of T-cell and HSPC therapies in the HIGM1 mouse model. Edited patients' derived CD4 T cells restored physiologically regulated CD40L expression and contact-dependent B-cell helper function. Adoptive transfer of wild-type T cells into conditioned HIGM1 mice rescued antigen-specific IgG responses and protected mice from a disease-relevant pathogen. We then obtained ~ 25% CD40LG editing in long-term repopulating human HSPC. Transplanting such proportion of wild-type HSPC in HIGM1 mice rescued immune functions similarly to T-cell therapy. Overall, our findings suggest that autologous edited T cells can provide immediate and substantial benefits to HIGM1 patients and position T-cell ahead of HSPC gene therapy because of easier translation, lower safety concerns and potentially comparable clinical benefits.
Topics: Animals; Gene Editing; Hematopoietic Stem Cells; Humans; Hyper-IgM Immunodeficiency Syndrome; Hyper-IgM Immunodeficiency Syndrome, Type 1; Mice; T-Lymphocytes
PubMed: 33475257
DOI: 10.15252/emmm.202013545 -
Journal of Otolaryngology - Head & Neck... Jun 2023Patients with chronic rhinosinusitis (CRS) and immunoglobulin deficiencies (ID) have more recalcitrant sinonasal disease and a subset of these patients undergo surgical...
BACKGROUND
Patients with chronic rhinosinusitis (CRS) and immunoglobulin deficiencies (ID) have more recalcitrant sinonasal disease and a subset of these patients undergo surgical management for their CRS. However, there is a paucity of literature on the surgical outcomes in this patient population and appropriate treatment algorithms for CRS in patients with ID. The objective of this study was to better elucidate the outcomes of endoscopic sinus surgery (ESS) in patients with ID in terms of disease-specific quality-of-life scores and the need for revision surgery.
METHODS
A case-control study was performed comparing adult patients with ID and healthy controls that had undergone ESS for CRS. Patients were matched based on age, sex, CRS phenotype, and preoperative Lund-Mackay score. The revision surgery rates, time to revision surgery, and changes in sinonasal outcome tests (SNOT-22) were evaluated.
RESULTS
Thirteen patients with CRS and ID were matched to 26 control patients with CRS. The revision surgery rate for cases and controls was 31% and 12%, respectively, but there was no statistical difference (p > 0.05). There was a clinically meaningful reduction in SNOT-22 scores in both groups from the preoperative to postoperative period [mean of 12 points in patients with ID (p = 0.323) and 25 points in controls (p < 0.001)], however, there was again no significant difference between cases and controls (p > 0.05).
CONCLUSION
Our data suggests that patients with ID have clinically meaningful improvement in SNOT-22 scores after ESS but may have higher revision rates than immunocompetent patients with CRS. ID are rare disease entities, thus most attempts at studying this cohort would be limited by sample size. Further homogenous data on immunoglobulin deficient patients is required for future meta-analysis to better understand the impact of ESS in patients with ID.
Topics: Humans; Algorithms; Case-Control Studies; Chronic Disease; Phenotype; Sinusitis; Dysgammaglobulinemia; Nasal Surgical Procedures; Endoscopy
PubMed: 37386535
DOI: 10.1186/s40463-023-00648-3 -
The Journal of Allergy and Clinical... Dec 2019Although chiefly a B-lymphocyte disorder, several research groups have identified common variable immunodeficiency (CVID) subjects with numeric and/or functional T cell... (Clinical Trial)
Clinical Trial
BACKGROUND
Although chiefly a B-lymphocyte disorder, several research groups have identified common variable immunodeficiency (CVID) subjects with numeric and/or functional T cell alterations. The causes, interrelationships, and consequences of CVID-associated CD4 T-cell derangements to hypogammaglobulinemia, autoantibody production, or both remain unclear.
OBJECTIVE
We sought to determine how circulating CD4 T cells are altered in CVID subjects with autoimmune cytopenias (AICs; CVID+AIC) and the causes of these derangements.
METHODS
Using hypothesis-generating, high-dimensional single-cell analyses, we created comprehensive phenotypic maps of circulating CD4 T cells. Differences between subject groups were confirmed in a large and genetically diverse cohort of CVID subjects (n = 69) by using flow cytometry, transcriptional profiling, multiplex cytokine/chemokine detection, and a suite of in vitro functional assays measuring naive T-cell differentiation, B-cell/T-cell cocultures, and regulatory T-cell suppression.
RESULTS
Although CD4 T cell profiles from healthy donors and CVID subjects without AICs were virtually indistinguishable, T cells from CVID+AIC subjects exhibited follicular features as early as thymic egress. Follicular skewing correlated with IgA deficiency-associated endotoxemia and endotoxin-induced expression of activin A and inducible T-cell costimulator ligand. The resulting enlarged circulating follicular helper T-cell population from CVID+AIC subjects provided efficient help to receptive healthy donor B cells but not unresponsive CVID B cells. Despite this, circulating follicular helper T cells from CVID+AIC subjects exhibited aberrant transcriptional profiles and altered chemokine/cytokine receptor expression patterns that interfered with regulatory T-cell suppression assays and were associated with autoantibody production.
CONCLUSIONS
Endotoxemia is associated with early commitment to the follicular T-cell lineage in IgA-deficient CVID subjects, particularly those with AICs.
Topics: Adolescent; Adult; B-Lymphocytes; Cell Differentiation; Child; Child, Preschool; Common Variable Immunodeficiency; Endotoxemia; Female; Humans; IgA Deficiency; Male; Middle Aged; T-Lymphocytes, Regulatory
PubMed: 31445098
DOI: 10.1016/j.jaci.2019.08.007 -
Frontiers in Immunology 2021Individuals with immunoglobulin G deficiency (IgGsd) often complain of fatigue. The correlation between systemic inflammation and fatigue is unknown. In this study...
PURPOSE
Individuals with immunoglobulin G deficiency (IgGsd) often complain of fatigue. The correlation between systemic inflammation and fatigue is unknown. In this study perceived quality of life (QoL) and fatigue in individuals with IgGsd, on and off immunoglobulin replacement therapy (IgRT) were correlated to inflammatory markers in plasma to identify the subgroup that benefits from IgRT.
METHOD
Thirty-five IgGsd-patients were sampled on three occasions: at baseline, after being on IgRT for at least 18 months, and 18 months after discontinuation of IgRT. Short form 36, EQ-5D-5L visual analogue scale and fatigue impact scale questionnaires were used for evaluation of QoL and fatigue. Furthermore, a panel of 92 inflammatory markers were analysed in plasma. Thirty-two gender- and age-matched healthy individuals were included as controls and sampled on one occasion.
RESULTS
QoL was lower and perceived fatigue higher in IgGsd compared to the controls. Severe fatigue and low QoL were associated with the need to restart IgRT (which is considered in IgGsd-individuals with a high burden of infections in Sweden). Twenty-five inflammatory factors were dysregulated in IgGsd and the plasma protein patterns were similar regardless of whether IgRT was ongoing or not. Enrichment analysis indicated IL-10 signalling as the most affected pathway. Severe fatigue was associated with decreased levels of the neurotrophic factors VEGFA and CSF-1.
CONCLUSION
Fatigue is a major contributory factor to impaired health-related QoL in IgGsd and is related to the need for IgRT. Low-grade systemic inflammation is a potential driver of fatigue. In addition to the burden of infections, we suggest the degree of fatigue should be considered when the decision to introduce IgRT is made.
Topics: Adult; Aged; Chemokine CXCL1; Chemokine CXCL5; Fatigue; Female; Humans; IgG Deficiency; Immunoglobulin G; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-10; Male; Middle Aged; Quality of Life; Surveys and Questionnaires; Sweden; Young Adult
PubMed: 35082787
DOI: 10.3389/fimmu.2021.797336 -
Journal of Clinical Immunology Feb 2021Patients with an IgG subclass deficiency (IgSD) ± specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with an IgG subclass deficiency (IgSD) ± specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective studies have shown that prophylactic antibiotics (PA) and immunoglobulin replacement therapy (IRT) can both be effective in preventing these infections; however, this has not been confirmed in a prospective study.
OBJECTIVE
To compare the efficacy of PA and IRT in a randomized crossover trial.
METHODS
A total of 64 patients (55 adults and 9 children) were randomized (2:2) between two treatment arms. Treatment arm A began with 12 months of PA, and treatment arm B began with 12 months of IRT. After a 3-month bridging period with cotrimoxazole, the treatment was switched to 12 months of IRT and PA, respectively. The efficacy (measured by the incidence of infections) and proportion of related adverse events in the two arms were compared.
RESULTS
The overall efficacy of the two regimens did not differ (p = 0.58, two-sided Wilcoxon signed-rank test). A smaller proportion of patients suffered a related adverse event while using PA (26.8% vs. 60.3%, p < 0.0003, chi-squared test). Patients with persistent infections while using PA suffered fewer infections per year after switching to IRT (2.63 vs. 0.64, p < 0.01).
CONCLUSION
We found comparable efficacy of IRT and PA in patients with IgSD ± SPAD. Patients with persistent infections during treatment with PA had less infections after switching to IRT.
CLINICAL IMPLICATION
Given the costs and associated side-effects of IRT, it should be reserved for patients with persistent infections despite treatment with PA.
Topics: Antibiotic Prophylaxis; Child; Female; Humans; IgG Deficiency; Immunoglobulin G; Immunologic Deficiency Syndromes; Male; Middle Aged; Persistent Infection; Primary Immunodeficiency Diseases
PubMed: 33206257
DOI: 10.1007/s10875-020-00841-3 -
Laboratory Medicine Nov 2017Measurement of IgG subclass concentrations is a standard laboratory test run as part of a panel to investigate the suspicion of antibody deficiency. The assessment is... (Review)
Review
Measurement of IgG subclass concentrations is a standard laboratory test run as part of a panel to investigate the suspicion of antibody deficiency. The assessment is clinically important when total IgG is within the normal age-specific reference range. The measurement is useful for diagnosis of IgG subclass deficiency, to aid the diagnosis of specific antibody deficiency, as a supporting test for the diagnosis of common variable immunodeficiency, as well as for risk stratification of patients with low IgA. The measurement of IgG subclasses may also help determine a revaccination strategy for patients and support patient management. In certain circumstances, the measurement of IgG subclasses may be used to monitor a patient's humoral immune system. In this review, we discuss the utility of measuring IgG subclass concentrations.
Topics: Common Variable Immunodeficiency; Dysgammaglobulinemia; Humans; Immunoglobulin A; Immunoglobulin G; Immunologic Deficiency Syndromes
PubMed: 29126302
DOI: 10.1093/labmed/lmx058 -
BMC Nephrology Nov 2020Angioimmunoblastic T cell lymphoma (AITL) is an infrequent hematological malignancy with variable and often atypical presentations. The presence of dysproteinemia,... (Review)
Review
Delayed diagnosis of Angioimmunoblast T-cell lymphoma presenting with type II Cryoglobulinemia and acute kidney injury: a case report and narrative review of the literature.
BACKGROUND
Angioimmunoblastic T cell lymphoma (AITL) is an infrequent hematological malignancy with variable and often atypical presentations. The presence of dysproteinemia, autoantibodies and systemic involvement in AITL has often led to a delay in diagnosis or even misdiagnosis in practice. We herewith present a case of AITL that primarily presented with acute kidney injury associated with type II Cryoglobulinemia, the underlying cause was only identified 8 months after the emergence of initial symptoms.
CASE PRESENTATION
A 67-year old woman presented with 2-month history of intermittent joint pain and a 3-day history of bilateral lower limb edema and acute kidney injury. Initial laboratory investigations showed marked hypocomplementemia with positive autoantibodies of ANA, anti-cardiolipin-IgM and direct antiglobulin. The serum and urinary Immunofixation and serum cryoglobulin tests were negative, while the serum free κ to λ light chain ratio was 0.231. A renal biopsy showed a diffuse proliferative glomerulonephritis with intracapillary pseudothrombi formation. There were orderly arranged microtubular structures of 20-35 nm in diameter in the subendothelial and mesangial area on electron microscopy. Shortly afterwards, the patient developed tingling affecting her finger tips and weak hands and legs. A diagnosis of cryoglobulinemia complicated with cryoglobulinemic glomerulonephritis and polyneuropathy was made. She responded well to methylprednisolone, plasma exchange and rituximab. However, 3 months later, she presented with generalized pruritic rash, weight loss, and inguinal lymphadenopathy. A subsequent inguinal excisional lymph node biopsy at month 8 revealed AITL as the underlying disease.
CONCLUSIONS
AITL and its associated B cell dysregulation can give rise to autoimmunity and cryoglobulinemia which may conceal itself as the underlying disorder. In various clinical scenarios of auto-immune diseases, it is advisable that the clinicians should take into consideration the multi-faceted lymphoma.
Topics: Acute Kidney Injury; Adult; Aged; Blood Chemical Analysis; Complement C3; Creatinine; Cryoglobulinemia; Cryoglobulins; Delayed Diagnosis; Female; Humans; Kidney; Lymphoma, T-Cell; Male; Middle Aged
PubMed: 33160311
DOI: 10.1186/s12882-020-02125-9