scholarly journals A major genetic determinant of autoimmune diseases is associated with the presence of autoantibodies in hypersensitivity pneumonitis

2020 ◽  
Vol 56 (2) ◽  
pp. 1901380 ◽  
Author(s):  
Ivette Buendía-Roldán ◽  
Luis Santiago-Ruiz ◽  
Gloria Pérez-Rubio ◽  
Mayra Mejía ◽  
Jorge Rojas-Serrano ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Hypersensitivity Pneumonitis ◽  
Clinical Manifestations ◽  
Significant Risk ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Ancestral Haplotype ◽  
Genetic Determinant ◽  
Circulating Autoantibodies ◽  
Organic Particles

BackgroundHypersensitivity pneumonitis is an immune-mediated disease triggered by exposure to organic particles in susceptible individuals. It has been reported that a subgroup of patients with hypersensitivity pneumonitis develops autoantibodies with or without clinical manifestations of autoimmune disease. However, the mechanisms involved in this process and the effect of the autoantibodies on clinical course in hypersensitivity pneumonitis is unknown. We evaluated the association between human leukocyte antigen (HLA) class II alleles and hypersensitivity pneumonitis patients with and without autoantibodies.Methods170 hypersensitivity pneumonitis patients were included. We analysed the presence of antinuclear antibodies, rheumatoid factor, anti-SSA/Ro, anti-SSB/La and anti-CCP at the time of diagnosis. In addition, in a subset of patients we evaluated anti-Scl-70, anti-neutrophil cytoplasmic antibody, and anti-DNA. HLA typing was performed using PCR sequence-specific primers in a high-resolution modality, including HLA-DRB1 and HLA-DQB1 loci. Statistical analysis was performed employing Epi-Info v7 and SPSS v20.Results60 hypersensitivity pneumonitis patients showed sera autoantibodies (HPAbs+), and 110 hypersensitivity pneumonitis patients did not (HPAbs−). The frequency of the allele HLA-DRB1*03:01 was remarkably increased in the HPAbs+ group (10.8% versus 0.45%; OR 30.14, 95% CI 3.83–237.1; p=1.65×10-4 after Bonferroni's correction). Likewise, we found that the haplotype DRB1*03:01-DQB1*02:01, which is part of the 8.1 ancestral haplotype, a major genetic determinant of autoimmune diseases, confers significant risk to develop autoantibodies (OR 19.23, 95% CI 2.37–155.9; p=0.0088 after Bonferroni's correction). In addition, the HLA-DRB1*03:01 allele was associated with higher mortality in patients with hypersensitivity pneumonitis (adjusted OR 5.9, 95% CI 1.05–33.05; p=0.043).ConclusionsA subset of hypersensitivity pneumonitis patients presents circulating autoantibodies and higher mortality that are associated with some alleles of 8.1 ancestral haplotype.

Graft-Versus-Host Disease (GVHD) in Cord Blood Transplantation (CBT): Risk Factors, Clinical Manifestations and Outcomes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2977-2977
Author(s):  
Daniel Couriel ◽  
Poliana Patah ◽  
Rima Saliba ◽  
Lawrence Cooper ◽  
Laura Worth ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cord Blood ◽  
Proportional Hazards ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Clinical Manifestations ◽  
Significant Risk ◽  
Cox Proportional Hazards ◽  
Hla Typing ◽  
Significant Difference

Abstract Introduction: Umbilical CBT from mismatched donors can restore hematopoiesis both in children and adults with acceptable rates of severe acute (aGVHD) and chronic GVHD (cGVHD). Acute and chronic GVHD, including risk factors, clinical manifestations and its specific impact on outcomes has not been systematically evaluated in this particular patient population. Objective: To analyze the manifestations of GVHD in CBT, with emphasis on risk factors and impact on overall survival. Methods: Prospective evaluation of aGVHD and cGVHD in 138 adult and pediatric patients undergoing single or double CBT for hematological disorders and solid tumors from 3/96 and 6/07. cord blood units were selected on the basis of a maximum of 2 MM (HLA-A, B, DRB1) and the minimum of 1x107TNC/Kg. Risk factors for aGVHD after CBT were assessed using the Cox proportional hazards method. The estimates of aGVHD and cGVHD were performed accounting for competing risks such as death and engraftment using the cumulative incidence (CI) method. Results: A total of 138 adult (n=78) and pediatric (n=60) CBT were performed in the time period. Median age was 21 (1-64), 58 females and 80 males. The majority received a transplant for hematological malignancies (n= 132), mostly MDS/AML and ALL (n= 98, 71%). The remainder had AA (n= 3) and one a solid tumor (n=1). Seventy-seven patients (56%) were in remission of their disease at the time of transplant. Most patients received a myeloablative regimen (n= 125, 91%), and single cord grafts (n= 81, 59%). Of 100 CBT where HLA typing is available, 39%, 45 and 9% have 1, 2 and 3 mismatched loci respectively. Twenty-four patients (17%) did not engraft. At 3 months post transplant, the CI of grade II-IV aGVHD was 36% (adult 38%, pediatric 34%, p= 0.9), and that of grade III-IV was 12% (adult 14%, pediatric 10%, p= 0.9). Skin was the organ most often involved (84%, adult 71%, pediatric 100%, p= 0.017). In adults skin was the only organ involved in 80% of patients with skin GVHD. Lower GI, upper GI and liver involvement were observed in 24, 18, and 21% of patients respectively, without significant difference between adults and children. The total nucleated cell count (TNC) of the graft was the strongest predictor of aGVHD. In children, active disease at the time of transplant was also significantly associated with higher incidence aGVHD. Other factors analyzed, including number and type of mismatched HLA loci were not significant risk factors for aGVHD. CI of cGVHD was 20%, and significantly lower in children compared to adults (8 vs 31%, p= 0.002). Nonrelapse mortality (NRM) at 2 years was 30%, and significantly lower in children (18 vs 41%, p= 0.007). Only 7/43 (16%) deaths were attributed to aGVHD or cGVHD. Conclusions: CBT can be performed in children and adults with acceptable rates of GVHD, even in the presence of multiple HLA mismatched loci. Most cases of acute GVHD involved the skin, often as the only organ. Chronic GVHD and NRM are significantly higher in adults. GVHD accounts for a relatively small proportion of nonrelapse deaths.

scholarly journals Celiac Disease Revisited

2021 ◽  
pp. 1-14
Author(s):  
João Calado ◽  
Mariana Verdelho Machado
Keyword(s):  
Celiac Disease ◽  
Systemic Disease ◽  
Human Leukocyte ◽  
Risk Groups ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Serological Tests ◽  
Leukocyte Antigen ◽  
Human Leukocyte Antigen Haplotype ◽  
Circulating Autoantibodies

Celiac disease (CD) is a systemic disease triggered by gluten ingestion in genetically predisposed individuals. It manifests primarily as an autoimmune enteropathy associated with specific circulating autoantibodies and a human leukocyte antigen haplotype (HLA-DQ2 or HLA-DQ8). It afflicts roughly 1% of the population, though the majority of patients remain undiagnosed. Diarrhea and malabsorption are classic manifestations of CD; however, both children and adults can be paucisymptomatic and present extraintestinal manifestations such as anemia, osteoporosis, and abnormal liver tests. CD screening is not recommended for the general population, and it should be focused on high-risk groups. CD diagnosis is challenging and relies on serological tests, duodenal histology, and genetic testing. Particularly difficult presentations to manage are seronegative patients, seropositive patients without villus atrophy, and patients who have started a gluten-free diet before the diagnostic workup. The only proven treatment is a lifelong gluten-free diet. We present an in-depth review on the physiopathology and management of CD, with a particular emphasis on diagnostic challenges.

scholarly journals Human Leukocyte Antigen and Red Blood Cells Impact Umbilical Cord Blood CD34+ Cell Viability after Thawing

2019 ◽  
Vol 20 (19) ◽  
pp. 4875 ◽  
Author(s):  
Vanegas ◽  
Galindo ◽  
Páez-Gutiérrez ◽  
González-Acero ◽  
Medina-Valderrama ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Cell Viability ◽  
Cord Blood ◽  
Red Blood Cells ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Blood Cells ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Leukocyte Antigen

Hematopoietic progenitor cell (HPC) transplantation is a treatment option for malignant and nonmalignant diseases. Umbilical cord blood (UCB) is an important HPC source, mainly for pediatric patients. It has been demonstrated that human leukocyte antigen (HLA) matching and cell dose are the most important features impacting clinical outcomes. However, UCB matching is performed using low resolution HLA typing and it has been demonstrated that the unnoticed mismatches negatively impact the transplant. Since we found differences in CD34+ viability after thawing of UCB units matched for two different patients (p = 0.05), we presumed a possible association between CD34+ cell viability and HLA. We performed a multivariate linear model (n = 67), comprising pre-cryopreservation variables and high resolution HLA genotypes separately. We found that pre-cryopreservation red blood cells (RBC), granulocytes, and viable CD34+ cell count significantly impacted CD34+ viability after thawing, along with HLA-B or -C (R2 = 0.95, p = 0.01; R2 = 0.56, p = 0.007, respectively). Although HLA-B*40:02 may have a negative impact on CD34+ cell viability, RBC depletion significantly improves it.

scholarly journals Non-tuberculous Mycobacterium Disease: Radiologic Manifestation in an Infant presenting with Respiratory Distress

2017 ◽  
Vol 5 (1-2) ◽  
pp. 13-20
Author(s):  
Rupesh Gautam ◽  
Maria Isabel Atienza ◽  
Maika Noda ◽  
Mariaem Andres
Keyword(s):  
Hypersensitivity Pneumonitis ◽  
Pulmonary Infection ◽  
Clinical Manifestations ◽  
Distinct Group ◽  
Middle Lobe ◽  
Air Trapping ◽  
Pulmonary Tb ◽  
Radiologic Findings ◽  
The Common ◽  
Common Manifestation

Non-tuberculous mycobacterium (NTM) comprises distinct group of organisms with lymphadenitis and pulmonary infection as the common manifestation. The diagnosis of pulmonary disease is based on clinical manifestations, radiologic findings and microbiologic culture. The classic NTM infection may be indistinguishable from pulmonary TB. Non-classic infection has predilection to the middle lobe and lingula unlike tuberculosis which is commonly seen in the upper lobes. The disease may also present as hypersensitivity pneumonitis with ground glass like opacities, centrilobular nodules and air trapping on imaging. The knowledge of imaging manifestations of NTM will aid in timely diagnosis and treatment of the disease.Nepal Journal of Radiology Vol.5(1-2) 2015: 13-20

scholarly journals Performance Characteristics of Updated INNO-LiPA Assays for Molecular Typing of Human Leukocyte Antigen A (HLA-A), HLA-B, and HLA-DQB1 Alleles

2004 ◽  
Vol 11 (2) ◽  
pp. 430-432 ◽  
Author(s):  
Karen De Vreese ◽  
Rachel Barylski ◽  
Fiona Pughe ◽  
Miriam Bläser ◽  
Colin Evans ◽  
...  
Keyword(s):  
Performance Evaluation ◽  
Human Leukocyte Antigen ◽  
Molecular Typing ◽  
Human Leukocyte ◽  
Performance Characteristics ◽  
Hla Typing ◽  
Tissue Typing ◽  
Leukocyte Antigen ◽  
Antigen A ◽  
Accuracy Rates

ABSTRACT We carried out a multicenter performance evaluation of three new DNA-based human leukocyte antigen (HLA) typing assays: INNO-LiPA HLA-A Update, INNO-LiPA HLA-B Update, and INNO-LiPA HLA-DQB1 Update. After optimization, the accuracy rates were all 100%, and the final observed resolutions were 99.4, 92.4, and 85.6%, respectively. These rapid and easy-to-perform assays yielded results fully concordant with other DNA-based tissue typing tests.

scholarly journals Clinical Manifestations and Mechanisms of Autoimmune Disease-Related Multiple Cerebral Infarcts

2019 ◽  
Vol 28 (8) ◽  
pp. 1045-1052
Author(s):  
Li-Li Sun ◽  
Wen-Xiong Tang ◽  
Min Tian ◽  
Lu Zhang ◽  
Zun-Jing Liu
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Transcranial Doppler ◽  
Clinical Manifestations ◽  
Cerebral Infarcts ◽  
Acute Infarction ◽  
Multiple Stroke ◽  
Underlying Mechanisms ◽  
Embolic Signals

It is important to investigate the clinical characteristics and identify the stroke mechanisms of patients with autoimmune disease-related stroke, which are necessary for early etiology diagnosis, accurate treatment and preventive strategies. In this article we retrospectively studied eight cases of acute ischemic stroke associated with autoimmune diseases, and without competing conventional stroke etiologies. The characteristics of stroke (clinical and radiological features), the laboratory tests especially serum D-dimer levels (as a marker of hypercoagulable state), and embolic signals on transcranial Doppler were evaluated for all eight patients. High-resolution magnetic resonance imaging (HRMRI), which can help to evaluate vasculitis was performed in four patients. The possible underlying mechanisms of these cases were discussed based on these manifestations. As a result, autoimmune diseases in our study included systemic lupus erythematosus ( n=5), mixed connective tissue disease ( n=1), central nervous system vasculitis ( n=1), and Takayasu arteritis ( n=1). All eight patients presented with acute infarction lesions in ≥2 vascular territories. Most patients presented with numerous small and medium infarction lesions located in the cortical and subcortical areas. Multiple stroke mechanisms were involved in these cases, including hypercoagulability ( n=4), cardiac embolism ( n=1) and vasculitis ( n=3). Embolic signals could be detected on transcranial Doppler in all three stroke mechanisms. In conclusion, our study revealed the characteristics of autoimmune disease-related stroke. For patients with multiple acute cerebral infarcts within non-single arterial territories, autoimmune disease is an important etiology not to be neglected. Multiple stroke mechanisms were involved in these cases.

scholarly journals A comparative review of use of sulphate and phosphate salts for colonoscopy preparations and their potential for nephrotoxicity

2018 ◽  
Vol 06 (10) ◽  
pp. E1206-E1213 ◽  
Author(s):  
Bruno Moulin ◽  
Thierry Ponchon
Keyword(s):  
Clinical Manifestations ◽  
Significant Risk ◽  
Distal Tubule ◽  
Kidney Damage ◽  
Calcium Excretion ◽  
Advantages And Disadvantages ◽  
Bowel Cleansing ◽  
Comparative Review ◽  
Phosphate Salts ◽  
Sulphate Salts

Abstract Background and study aims Colonoscopy is a widely used diagnostic procedure which requires prior cleansing of the bowel. Many different bowel cleansing preparations have been developed, all of which have specific advantages and disadvantages. This review compares two low-volume high-osmolarity bowel cleansing preparations, oral phosphate salts and oral sulphate salts, with a particular focus on risk of nephrotoxicity. Patients and methods An electronic search of the Medline database was performed using the search terms “(phosphates OR sulfates) AND cathartics [MeSH Term] AND kidney” restricted to humans with a cut-off date of December 31, 2016. Results Introduction of oral phosphate salts offered the advantage of low intake volume and low risk of bowel irritation compared to previous options. However, phosphate salts have been associated with renal toxicity (acute phosphate nephropathy [APN]), thought to arise due to perturbations of calcium and phosphate homeostasis as a consequence of increases in serum phosphate. This results in high concentrations of calcium phosphate in the distal tubule and collecting ducts of the kidney, where it may precipitate. Although APN is rare, it may lead to permanent kidney damage. For this reason, phosphate salts are contraindicated in vulnerable patient groups. As an alternative to phosphate salts, oral sulphate salts have recently been introduced. Because sulphate absorption from the intestinal tract is saturable, serum sulphate concentrations increase only minimally after ingestion. Furthermore, excretion of sulphate in the kidney is not accompanied by calcium excretion and urine calcium levels are unchanged. For these theoretical reasons, use of sulphate salts as bowel cleansing solutions is not expected to lead to calcium precipitation in the nephron. Conclusions Oral phosphate salts are no longer recommended for routine use as bowel cleansing preparations as they carry significant risk of kidney damage and a safer alternative is available in the form of oral sulphate solutions. To date, use of sulphate salts has not been associated with elevations in serum creatinine or other markers of renal impairment, nor with clinical manifestations of kidney injury. Nonetheless, experience with sulphate salts in everyday practice is limited and physicians should be vigilant in detecting potential safety issues.

scholarly journals Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Paola Cruz-Tapias ◽  
Oscar M. Pérez-Fernández ◽  
Adriana Rojas-Villarraga ◽  
Alberto Rodríguez-Rodríguez ◽  
María-Teresa Arango ◽  
...  
Keyword(s):  
Risk Factor ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Genetic Characteristics ◽  
Latin Americans ◽  
Leukocyte Antigen

The prevalence and genetic susceptibility of autoimmune diseases (ADs) may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA) class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1∗03:01 (OR: 4.04; 95%CI: 1.41–11.53) was found to be a risk factor for systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and type 1 diabetes mellitus (T1D). DRB1∗04:05 (OR: 4.64; 95%CI: 2.14–10.05) influences autoimmune hepatitis (AIH), rheumatoid arthritis (RA), and T1D; DRB1∗04:01 (OR: 3.86; 95%CI: 2.32–6.42) is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS) and T1D. DQB1∗06:02 and DRB1∗15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1∗06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.

Sign in / Sign up

Export Citation Format

Share Document