Superior survival associated with transplantation of matched unrelated versus one-antigen–mismatched unrelated or highly human leukocyte antigen– disparate haploidentical family donor marrow grafts for the treatment of hematologic malignancies: establishing a treatment algorithm for recipients of alternative donor grafts

Blood ◽  
2002 ◽  
Vol 99 (3) ◽  
pp. 806-814 ◽  
Author(s):  
William R. Drobyski ◽  
John Klein ◽  
Neal Flomenberg ◽  
Daniel Pietryga ◽  
David H. Vesole ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Treatment Algorithm ◽  
Human Leukocyte ◽  
Hematologic Malignancies ◽  
Unrelated Donor ◽  
Leukocyte Antigen ◽  
Significant Difference ◽  
Family Donor

Abstract The purpose of this study was to compare transplantation outcomes in patients with hematologic malignancies who received marrow grafts from either phenotypically matched unrelated, one- antigen–mismatched unrelated, or highly human leukocyte antigen (HLA)–disparate family donors. Between 1993 and 2000, 139 patients underwent transplantation from unrelated donors (81 matched and 58 mismatched) and 48 patients received marrow grafts from family donors that were mismatched at 2, 3, or 4 of 8 HLA loci. All patients received a standardized conditioning regimen and a graft-versus-host disease (GVHD) prophylaxis schedule with the exception of recipients of haploidentical marrow grafts, who received antithymocyte globulin after bone marrow transplantation as additional immunosuppression. There was no statistically significant difference in the rate of engraftment, or the cumulative incidences of acute and chronic GVHD between any of the 3 groups. The 2-year cumulative incidence of relapse was lower in matched unrelated patients (25%, P = .01) and mismatched unrelated patients (26%,P = .014) than in haploidentical patients (42%). Transplant-related mortality was significantly higher in recipients of mismatched unrelated grafts (45%, P = .01) and haploidentical grafts (42%, P = .001) compared with recipients of matched unrelated marrow grafts (23%). This resulted in a significantly higher probability of overall survival for matched unrelated patients (58%) versus either mismatched unrelated (34%,P = .01) or haploidentical (21%, P = .002) patients. There was no statistically significant difference in survival between patients who received mismatched unrelated grafts versus those who received haploidentical grafts. This study supports a donor selection algorithm whereby patients who lack a closely matched family donor be offered a phenotypically matched unrelated donor if available. There is no apparent advantage to using a mismatched unrelated versus a highly HLA-disparate family donor.

Significance of a Single Human Leukocyte Antigen Mismatch on the Outcome of Nonmyeloablative Allogeneic Stem Cell Transplantation from Related Donors Using the Mexican Schedule.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5182-5182
Author(s):  
Guillermo J. Ruiz-Arguelles ◽  
Briceida López-Martínez ◽  
Carlos Manzano ◽  
J. D. Gómez-Rangel
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Human Leukocyte Antigen ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Nonmyeloablative Stem Cell Transplantation ◽  
Number Of Patients

Abstract The Mexican approach was used to conduct nonmyeloablative stem cell transplantation (SCT) in patients with various malignant and non-malignant hematologic diseases. Patients received a modified, low-intensity conditioning regimen, which included oral busulphan 4 mg/kg on Days −6 and −5, IV cyclophosphamide 350 mg/m2 on Days −4, −3, and −2, IV fludarabine 30 mg/m2 on Days −4, −3, and −2, oral cyclosporine A 5 mg/kg twice daily staring on Day −1 (continuing until Day 180), and IV methotrexate 5 mg/m2 on Days +1, +3, +5, and +11. Allografts were prospectively performed in 58 patients using sibling donors that were either human leukocyte antigen (HLA) identical (6/6) or compatible with 1 mismatch (5/6). In allografts where the donor was an HLA identical sibling (n = 40), the median overall survival was 33 months compared to 8 months when the donor was an HLA compatible sibling (n = 18; P <.01). The 52-month survival was 47% versus 38% in patients receiving allografts from HLA-identical donors and HLA-compatible donors, respectively. The prevalence of acute graft-versus-host-disease (GVHD) was 57% versus 38%, the prevalence of chronic GVHD was 25% versus 11%, and the relapse rate was 45% versus 55% in patients receiving allografts from HLA-identical donors and HLA-compatible donors, respectively. Two patients failed to engraft; both were 5/6 matches. Despite a trend toward less favorable results in patients allografted from HLA compatible (5/6) siblings, most differences in outcome were not significant, likely due to the small number of patients in the study. These data suggest that nonmyeloablative SCT using the Mexican approach may be a valid option for individuals with either an HLA identical or HLA compatible sibling donor.

scholarly journals Non-inherited maternal human leukocyte antigen alleles in susceptibility to familial rheumatoid arthritis

2008 ◽  
Vol 68 (1) ◽  
pp. 107-109 ◽  
Author(s):  
K A Guthrie ◽  
N R Tishkevich ◽  
J L Nelson
Keyword(s):  
Rheumatoid Arthritis ◽  
Human Leukocyte Antigen ◽  
Age Of Onset ◽  
Human Leukocyte ◽  
Paternal Allele ◽  
Hla Alleles ◽  
Leukocyte Antigen ◽  
The North ◽  
Significant Difference ◽  
Hla Genotype

Objectives:Some patients with rheumatoid arthritis (RA) lack RA-associated human leukocyte antigen (HLA) alleles. Prior studies investigated non-inherited maternal HLA alleles (NIMA) in RA risk with conflicting results.Methods:We examined NIMA in a large cohort of families from the North American Rheumatoid Arthritis Consortium (NARAC).Results:Among 620 patients with 1 or both parents having a HLA genotype, patients with RA informative for analysis included 176 without HLA-DRB1*04 and 86 without the HLA shared epitope (SE). The frequency of NIMA encoding HLA-DR4 or the SE was compared to the non-inherited paternal allele (NIPA). DR4-encoding NIMA vs NIPA revealed no significant difference (27% vs 20%). However, parity is known to modulate RA risk and analyses stratified by sex and age of onset showed significant variation among women. Interestingly, among women with onset <45 years DR4-encoding NIMA was increased compared to NIPA; among women ⩾45 years at onset the reverse was observed (31% vs 16% compared to 10% vs 60%, p = 0.008). DR4 encoding NIMA vs NIPA did not differ in men. The SE did not differ in men or women.Conclusions:Risk of RA was associated with HLA-DR4 encoding NIMA in younger-onset women but not in older-onset women or men. These observations could help explain conflicting prior results of NIMA in RA.

Primary Graft Failure (GF) after Unrelated Donor Cord Blood Transplants (UCBT): Risk Factors and Management.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 44-44 ◽  
Author(s):  
Ka Wah Chan ◽  
Michael S. Grimley ◽  
Candace Taylor ◽  
Donna A. Wall
Keyword(s):  
Risk Factors ◽  
Cord Blood ◽  
Aplastic Anemia ◽  
Bone Marrow Failure ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Viral Reactivation ◽  
Unrelated Donor ◽  
Cell Dose

Abstract Primary GF is recognized as a major risk in UCBT. Both graft (cell dose and quality of the cord blood unit) and recipient (diagnosis of aplastic anemia, prior chemotherapy exposure) characteristics have been reported as being associated with non-engraftment. Here we present a large series of UCBT patients from a single institution and analyze the risk factors and management of this complication. Between 3/2001 and 7/2006, 106 consecutive patients (pts), of median age 5.3 (range 0.1–18.4) years and weight median 22 (range 4–85) kg, received UCBT at Texas Transplant Institute. 13 did not achieve donor engraftment as documented by recovery of ANC&lt; 500/μl by day + 42, and lack of donor cells on ≥2 RFLP analysis of the bone marrow. Failure to attain engraftment occurred in 5/27 with a non-malignant disorders, and 8/79 with hematologic malignancies (p&lt; 033). Non-engraftment was less common in better HLA matched transplants (≥5/6 HLA match: 1/45 vs ≤ 4/6 HLA : 12/61; p&lt; 0.02). Preliminary analysis showed no difference in cord blood TNC/kg, CD34/kg and pre thaw CFU/kg in pts who had primary GF compared to the rest of the cohort. A post thaw CFU/pre-freeze ratio of &lt;20% was more common in primary GF. Among the 79 pts with hematologic malignancies (HM), 8 did not engraft. 4 died early; 1 from persistent leukemia, and 3 from transplant-related complications (TRM). Of the remaining 4 pts with HM, 2 were ALL children in CR1. The other primary GF occurred in 2/5 children with HLH (both with active disease at UCBT), 2/8 the children transplanted for aplastic anemia, and one pt with CD40L deficiency who had primary GF. The 9 pts who had not relapsed or died of TRM went on to second (2nd) UCBT 33 to 95 (median 55) days after first transplant (1st UCBT). Conditioning regimen for 2nd UCBT was fludarabine 175mg/m2, cyclophosphamide 50mg/kg, TBI 2 Gy, ± ATG in 7/9 patients. Median cell dose for 2nd UCBT were 3.6 × 107/kg. HLA matching was similar to 1st UCBT. There was one TRM (respiratory failure) but the rest (8/8) engrafted; with ANC &gt;500/μl at a median of 15 (range 5–64) days, and platelets &gt; 20000/μl at a median of 92 (range 24 to 137) days. All became transfusion-independent, and as of 8/1/2006, 7 of 9 pts are alive. All have complete donor chimerism 164–1616 (median 672) days after 2nd UDCBT. EBV-lymphoproliferatve disorders developed in 2 patients and it was fatal in one. Other viral infections encountered were BKV(1), HHV-6(1), CMV(3) in the blood; adenovirus(1) and enterovirus(1) in the stool; and BKV (1) in the urine. Acute graft-versus-host disease (GVHD) was diagnosed in 2/8 pts. 7/8 pts surviving &gt;100 days had chronic GVHD, and it was extensive in 5 pts. It is important that primary GF be recognized as a risk of UDCBT and a back-up donor source be identified prior to transplant. Children with intact/active immune systems prior to transplant are at greater risk. Early 2nd UCBT, before patient’s condition deteriorates, is a feasible treatment alternative. This immunosuppressive preparative regimen is well tolerated early post first UCBT and can result in reliable engraftment, albeit a greater risk of chronic GVHD and viral reactivation post transplant.

A Randomized 3-Arm Phase II Study to Determine the Most Promising Postgrafting Immunosuppression for Prevention of Acute Graft-Versus-Host Disease (GVHD) After Unrelated Donor Hematopoietic Cell Transplantation (HCT) Using Nonmyeloablative Conditioning for Patients with Hematologic Malignancies: A Multi-Center Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 348-348 ◽  
Author(s):  
Brenda M. Sandmaier ◽  
Michael Maris ◽  
Barry Storer ◽  
Lars Vindelov ◽  
Amelia Langston ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Phase Ii ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematologic Malignancies ◽  
Unrelated Donor ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Sequential Trials

Abstract Abstract 348 We previously reported results of 3 sequential trials of GVHD prophylaxis with mycophenolate mofetil (MMF) BID/TID and cyclosporine (CSP) BID with various taper schedules in patients (pts) with advanced hematologic malignancies given unrelated G-CSF-mobilized peripheral blood stem cell (PBSC) grafts after fludarabine 90 mg/m2 and 2 Gray total body irradiation. Cumulative incidences of grades II-IV acute GVHD in the 3 trials were 52, 53 and 77%, respectively. The goal of the current protocol was to evaluate, in a phase II randomized 3-arm study, which drug combination or schedule was most promising in preventing acute GVHD. Tacrolimus (Tac) was used in place of CSP and each of the 3 arms used MMF TID until day 30 and then BID, but the subsequent duration of MMF varied. In Arm1, pts received Tac until day 180 and MMF until day 96. In Arm2, Tac was given until day 150 and MMF until day 180. In Arm3, Tac was given until day 150 and MMF until day 180 with the addition of rapamycin from days -3 through 80. One hundred seventy-five pts ineligible for myeloablative conditioning were enrolled on this multi-institutional study between Jan/05 and Aug/09, and results on the first 159 pts (Arm1 n=56; Arm2 n=51; Arm3 n=52) are reported here with a median follow-up of 18.4 months for surviving pts. The median age of pts was 60 (range 13-75) yrs. Sixty-six (42%) had previous autologous (n=55) or allogeneic (n=11) HCT. All pts were matched for HLA-DRB1 and -DQB1 at the allele level: 16 had single allele mismatches at HLA-A, -B or –C and the remainder (n=143) were fully HLA-matched. Diagnoses included AML (n=72), NHL (n=36), MM (n=19), ALL (n=10), CLL (n=9), MDS (n=8), HL (n=4), and CML (n=1). Randomization was based upon transplant center (FHCRC vs other), number of prior chemotherapy treatments (0-2 vs 3+), and age (<55 vs 55+ years). The pts received PBSC grafts containing a median of 7.9 ×106 CD34 and 2.8 × 108 CD3 cells/kg. Sustained donor engraftment occurred in 99.4% of pts. The day-150 cumulative incidences of grades II-IV (figure 1) and III-IV acute GVHD were as follows: Arm1: 56%, 9%; Arm2: 52%, 12%; and Arm3: 45%, 10%, respectively. Chronic GVHD requiring therapy was as follows: Arm1: 44%, Arm2: 35%, and Arm3: 55% of pts. The 6-month nonrelapse mortality was 6% in Arm1, 8% in Arm2, and 2% Arm3. The 2-year Kaplan-Meier estimates of relapse and nonrelapse mortality (figure 2) were as follows: Arm1: 27%, 24%; Arm2: 39%, 19%; and Arm3: 30%, 15%, respectively (overall 32% and 20%, respectively). The 2-year overall and progression-free survivals were as follows: Arm1: 49%, 41%; Arm2: 42%, 37%; Arm3: 55%, 41%, respectively (overall 48% and 40%, respectively). The addition of rapamycin to MMF and Tac (Arm3) resulted in the lowest incidence of grades II-IV acute GVHD (p=0.09 compared to reference Arm1), without a significant difference in chronic GVHD. While the phase II design of the study was not powered to show statistical differences between the 3 arms, the lower incidence of grades II-IV acute GVHD combined with the low morbidity and nonrelapse mortality in Arm3 using MMF, Tac and rapamycin is encouraging and warrants further study. Disclosures: Off Label Use: Fludarabine - conditioning prior to HCT. Mycophenolate mofetil - immunosuppression after HCT. Tacrolimus - immunosuppression after HCT. Rapamycin - immunosuppression after HCT..

Allogeneic Bone Marrow Transplantation From HLA Mismatched Family Donors in Children with Aplastic Anemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 831-831 ◽  
Author(s):  
Hideki Muramatsu ◽  
Hiromasa Yabe ◽  
Ryoji Kobayashi ◽  
Akira Kikuchi ◽  
Kazuko Kudo ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Chronic Gvhd ◽  
Secondary Malignancy ◽  
Unrelated Donor ◽  
Allogeneic Bone ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Unrelated Donors ◽  
Related Donor ◽  
Family Donor

Abstract Abstract 831 The first-line therapy for children with severe aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-matched family donor, and immunosuppressive therapy (IST) is indicated for patients without HLA-matched family donors. While the standard therapy for children who fail to respond to IST is allogeneic HSCT from an HLA-matched unrelated donor, HSCT from an HLA-mismatched family donor has also been indicated. Compared with unrelated donors, an HLA-mismatched family donor has some advantages especially for children who need urgent transplantation. We analyzed the clinical outcome of 578 children (325 boys and 253 girls) with AA (age, <20 years) who received allogeneic BMT between 1990 and 2009 in Japan, and registered to the Transplant Registry Unified Management Program (TRUMP). The median age at transplantation was 11 years (0–19), and the donors were serological 6/6 HLA-matched related donors (MRD) (n = 312), 1 locus-mismatched related donor (1MMRD) (n = 44), 2–3 loci-mismatched related (haploidentical) donors (n = 9), and HLA-matched unrelated donors (MUD) (n = 213). Causes of deaths were as follows: acute graft-versus-host disease (GVHD) (n = 4), chronic GVHD (n = 4), acute respiratory distress syndrome (n = 2), severe hemorrhage (n = 7), engraftment failure (n = 5), infection (n = 18), idiopathic pneumonia (n = 8), organ failure (n = 19), secondary malignancy (n = 4), and others (n = 4). The probability of severe acute GVHD (grade III–IV) in patients transplanted from 1MMRD (26.9% ± 7.4%) was significantly higher than that in patients transplanted from MRD (4.9% ± 1.3%) (p < 0.001). The probability of 5-year overall survival (5y OS) of patients transplanted from 1MMRD (93.1% ± 3.9%) was comparable to that of patients transplanted from MRD (93.1% ± 1.5%) (p = not significant, NS), but it was significantly better than that of patients transplanted from haploidentical donors (66.7% ± 15.7%, p =.016) and MUD (79.0% ± 2.9%, p =.014). In the subgroup analysis of 1MMRD, no significant difference was observed between HLA class I-mismatched (n = 32) and class II-mismatched patients (n = 12) (5y OS; 93.8% ± 4.3% vs. 91.7% ± 8.0%, p = NS). Comparison of the survival outcome based on the transplant period (1990–1999 vs. 2000–2009) revealed that the probability of 5y OS of patients transplanted from 1MMRD was not significantly different (92.3% ± 5.2% (n = 26) vs. 94.4% ± 5.4% (n = 18), p = NS), while that of patients transplanted from MUD significantly improved in the same period as we reported previously (67.1% ± 5.5% (n = 73) vs. 86.1% ± 3.1% (n = 140), p =.001)(Yagasaki et al., Blood 2011). In multivariate analysis, haploidentical donors (p <.001), MUD (p <.001), age ≥ 10 years (p <.001), and transplant period (1990–1999 vs. 2000–2009, p =.006) were identified as independent covariates associated with unfavorable OS. In summary, our analysis revealed that an HLA-mismatched related donor, especially 1MMRD, could be selected as a donor candidate for children with AA who need urgent transplantation. Disclosures: No relevant conflicts of interest to declare.

Prevalence of human leukocyte antigen-B27 supertype in the context of positively charged neoepitopes and association with PD-L1 as an immune escape mechanism.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3083-3083
Author(s):  
Charlene Marie Fares ◽  
Amy Lauren Cummings ◽  
Matthew Karl Theisen ◽  
Jaklin Gukasyan ◽  
Jackson P Lind-Lebuffe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Leukocyte Antigen ◽  
Squamous Cell ◽  
Immune Escape ◽  
Immune Surveillance ◽  
Human Leukocyte ◽  
Immune Checkpoint Blockade ◽  
Leukocyte Antigen ◽  
Significant Difference ◽  
Positively Charged

3083 Background: Recent evidence suggests efficacy of immune checkpoint blockade may be influenced by human leukocyte antigen (HLA)-B. HLA-B27 supertype has an electronegative binding pocket which favorably binds and displays neoepitopes harboring positively charged amino acids (AAs). Based on immune surveillance, we postulate that B27 tumors that have favorable neoepitopes should face negative selective pressure, and B27 tumors with favorable neoepitopes that develop could be more likely to upregulate immune escape mechanisms. Here we evaluate the relationship between prevalence of B27 and positively charged neoepitopes and assess association between positively charged neoepitopes and expression of PD-L1. Methods: TCGA datasets from head and neck squamous cell (HNSC), lung squamous cell (LUSC), and melanoma (SKCM) patients were evaluated. HLA alleles were determined with OptiType and supertype was based on 2008 criteria. Nonsynonymous mutations were annotated with Ensembl VEP and VAtools. pVAC-Seq using NetMHCpan algorithm predicted neoepitopes 9 AAs in length. Favorable B27 neoepitopes were defined as those having new positively charged AA substitutions (H/K/R) from negative or uncharged wildtype AAs. RNA-seq data for the PD-L1 gene were normalized on transcripts per million and log2 transformed. Linear regression tests were performed between PD-L1 gene expression values and fraction of nonsynonymous mutations resulting in neoepitopes with new positively charged AAs in patients with B27. Results: Data from 497 HNSC, 494 LUSC, and 468 SKCM patients were analyzed. B27 was observed in 20.1%, 23.2%, and 26.5% of HNSC, LUSC, and SKCM patients, respectively, with a significant difference seen between HNSC and SKCM by chi-square test (χ² = 5.14, p = .023). Of new charged AAs resulting from nonsynonymous mutations, 76.3% in HNSC, 74.0% in LUSC, and 72.0% in SKCM were positively charged (p < .05 between all histologies, paired t-tests). In B27 patients, association between PD-L1 gene expression and fraction of neoepitopes with new positively charged AAs was seen in HNSC (r = 0.25 p = .036) and SKCM (r = 0.30 p = .007), but not LUSC (r = -0.12 p = .296). Conclusions: With increasing fraction of positively charged neoepitopes, a decrease in prevalence of B27 was observed, suggesting improved binding and immune elimination of tumors with favorable neoepitopes. In B27 tumors that develop despite having favorable neoepitopes, upregulation of PD-L1 could be a putative mechanism to evade immune detection.

scholarly journals HLA mismatch direction in cord blood transplantation: impact on outcome and implications for cord blood unit selection

Blood ◽  
2011 ◽  
Vol 118 (14) ◽  
pp. 3969-3978 ◽  
Author(s):  
Cladd E. Stevens ◽  
Carmelita Carrier ◽  
Carol Carpenter ◽  
Dorothy Sung ◽  
Andromachi Scaradavou
Keyword(s):  
New York ◽  
Human Leukocyte Antigen ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Human Leukocyte ◽  
Hematologic Malignancies ◽  
Leukocyte Antigen ◽  
Blood Transplantation ◽  
Cord Blood Unit ◽  
Unrelated Cord Blood

AbstractDonor-recipient human leukocyte antigen mismatch level affects the outcome of unrelated cord blood (CB) transplantation. To identify possible “permissive” mismatches, we examined the relationship between direction of human leukocyte antigen mismatch (“vector”) and transplantation outcomes in 1202 recipients of single CB units from the New York Blood Center National Cord Blood Program treated in United States Centers from 1993-2006. Altogether, 98 donor/patient pairs had only unidirectional mismatches: 58 in the graft-versus-host (GVH) direction only (GVH-O) and 40 in the host-versus-graft or rejection direction only (R-O). Engraftment was faster in patients with GVH-O mismatches compared with those with 1 bidirectional mismatch (hazard ratio [HR] = 1.6, P = .003). In addition, patients with hematologic malignancies given GVH-O grafts had lower transplantation-related mortality (HR = 0.5, P = .062), overall mortality (HR = 0.5, P = .019), and treatment failure (HR = 0.5, P = .016), resulting in outcomes similar to those of matched CB grafts. In contrast, R-O mismatches had slower engraftment, higher graft failure, and higher relapse rates (HR = 2.4, P = .010). Based on our findings, CB search algorithms should be modified to identify unidirectional mismatches. We recommend that transplant centers give priority to GVH-O-mismatched units over other mismatches and avoid selecting R-O mismatches, if possible.

scholarly journals Lack of association between diabetic nephropathy and human leukocyte antigen type 2 (HLA II-DQ1) in patients with type 2 diabetes mellitus in west of Iran

2020 ◽  
Vol 10 (4) ◽  
pp. e34-e34
Author(s):  
Mahsa Mohammadi ◽  
Mohsen Rajabnia ◽  
Mohammad Saad Forghani ◽  
Khaled Rahmani ◽  
Mohammad Bahadoram
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Diabetes Type 2 ◽  
Diabetes Type ◽  
Expression Levels ◽  
Leukocyte Antigen ◽  
Significant Difference

Introduction: Diabetic nephropathy (diabetic kidney disease) is one of the microvascular complications of diabetes mellitus. The human leukocyte antigen (HLA) is a group of genes that is related to autoimmune diseases, infections and inflammation. Studies regarding the association of type 2diabetes and HLA-II are negligible. Objectives: The aim of this study is to determinate association between diabetic nephropathy and HLA II-DQ1 in diabetes type 2 patients. Patients and Methods: In this study, 120 diabetes type 2 patients were divided into two groups of diabetic nephropathy (case group) and without diabetic nephropathy (control group). Blood samples were taken and DNA was isolated. Asymmetric polymerase chain reaction (PCR) was used to amplify the HLA II-DQ1 exon 2 and exon 3. PCR products were hybridized and labeled with probes on the chip. Determination of HLAII-DQ1 gene typing was conducted by scanning hybrid products and analyzed with PerkinElmer ScanArray software. Results: The results of chi-square test showed no significant difference between expression levels of HLA in the two groups (P<0.05). Conclusion: There was no significant difference between expression levels of HLA in two groups of patients. Various factors such as demographic characteristics, lifestyle, geographic region, and race are the factors influencing the relationship between diabetic nephropathy and DQ1-HLA II. Since this study is conducted in one region and one race and with limited population, it is suggested that future studies should be considered and the association between the mentioned variables with HLA should be considered.

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