Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HLA-A, -B, -C, and DR antigens were determined in 33 patients with sickle cell disease (SCD), who had received red blood cell (RBC) transfusions. Twenty-one patients formed red cell alloantibodies after transfusions (responders) while 12 multitransfused SCD patients did not form any RBC antibodies (non-responders). We found that 67% of the SCD responder participants had HLA-B35 versus 25% of the non-responders (chi 2 = 5.3079, P = 0.0212). The frequency of B35 in non-responder SCD patients was similar to that of a normal healthy Black population consisting of 139 individuals. Calculation of the relative risk showed that sickle cell patients with B35 are six times more likely to form RBC alloantibodies after transfusion than those lacking that HLA antigen. We found no significant increase or association between any HLA-DR antigens and sickle cell disease.
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PMID:HLA-B35 is associated with red cell alloimmunization in sickle cell disease. 348 40

Cerebral infarction occurs in one quarter of all children with sickle cell anemia (SCA). There is an increased risk of stroke in siblings with SCA, suggesting genetic factors may influence risk of stroke. The authors investigated whether HLA type was associated with risk of stroke in children with SCA. Fifty-three patients with SCA underwent complete HLA typing at both HLA class I (HLA-A, B) and HLA class II (HLA-DR, DQ, DP) loci. Of the 53 patients, 22 had magnetic resonance imagining (MRI)-documented evidence of cerebral infarction, and the remaining 31 patients had negative MRI scans. Comparison of the results of HLA typing between the SCA patients with a positive and those with a negative MRI documented that the 2 groups differed with respect to the class I HLA-B (P =.012), and the class II HLA-DRB1 (P =.0008) and DQB1 (P =.029). Susceptibility associations at the HLA-DRB1 locus included both DR3 alleles, where DRB1*0301 and *0302 were both associated with an increased risk of stroke. Protective associations were found in the DR2 group, where DRB1*1501 was protective for stroke. DQB1*0201, which is in linkage disequilibrium with DRB1*0301, was also associated with stroke. Similarly, DQB1*0602, in linkage disequilibrium with DRB1*1501, was protective. Specific HLA alleles may influence the risk of stroke in children with SCA. HLA typing may prove useful in identifying SCA patients at higher risk for stroke.
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PMID:Evidence for HLA-related susceptibility for stroke in children with sickle cell disease. 1082 44

In 2002, OPTN/UNOS altered kidney allocation rules to allow patients to be listed separately to receive kidneys from expanded criteria donors (ECD). Our aim was to quantify the short- and long-term impacts of 21 prognostic factors on recipients of ECD as well as recipients of living (LD) and deceased standard criteria (SCD) donors. A factor's impact depends on both the risk and diversity of its effects. Using OPTN/UNOS Registry data from 1996-2003, we have analyzed kidney-only, adult-recipient grafts for factor effects among 35,878 LD, 47,941 SCD and 10,399 ECD transplants. During an early risk period, all 94,218 recipients were followed through one year, and, in the late risk period, 85,270 recipients whose grafts survived beyond one year were followed for 5 years post-transplant. Impact was measured by determining a factor's percentage of assignable variation in one- and 5-year graft failure rates. Scores for 21 factors were estimated via generalized logistic models, which contained a random component for transplant center. The assignable variation associated with a given factor was computed as the factor score variance multiplied by the square of the corresponding regression coefficient. Impacts were heterogeneous with regard to posttransplant period and donor type. The top 5 factors influencing one-year graft survival rates were as follows: * For LD grafts - pretransplant dialysis time (14% of the variation in short-term outcomes), recipient age (13%), body mass (12%), PRA (10%) and induction therapy (10%). * For SCD grafts - donor age (24%), recipient age (12%), pretransplant dialysis time (12%), HLA-DR matching (6%) and pretransplant medical condition (6%). * For ECD grafts - donor age (18%), pre-transplant dialysis time (10%), recipient age (10%), pretransplant medical condition (10%) and recipient body mass (6%). Ranking long-term outcomes demonstrated the following top 5 influential factors: * For LD grafts - donor age (28% of the variation in long-term outcomes), recipient race (15%), age (15%), transplant year (13%) and recipient sex (11%). * For SCD grafts - donor age (35%), recipient race (23%), transplant year(15%), recipient sex (8%)and age (5%). * For ECD grafts - donor age (33%), recipient sex (20%), race (15%), transplant year (8%) and recipient's original disease (5%). Donor age was the dominant factor governing the survival rates among deceased donor kidney transplants. Advancing donor age was still the major risk factor for SCD transplant failure despite setting aside all donors 60 and up, and a large fraction of 50-59 year-old donors, from this group. Current ECD/SCD definitions warrant review and possible revision.
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PMID:Explainable variation in renal transplant outcomes: a comparison of standard and expanded criteria donors. 1670 59

The 10-year graft survival rates for first renal transplants performed during 1990-1994 and 1995-1999 and reported to the OPTN/UNOS Renal Transplant Registry increased from 57-58% for living donor transplants, from 42-46% for deceased donors aged 60 or under, and from 22-28% for donors over age 60 comparing the 2 intervals. These modest increases were accompanied by a 2% decline in 10-year patient survival for recipients of living and younger deceased donor grafts and a 1% improvement in patient survival for recipients of older donor kidneys. The 5-year graft and patient survival rates for transplants performed between 2000 and 2004 were 80% and 90% for living donor, 69% and 90% for standard criteria deceased donor and 55% and 82% for expanded criteria donor transplants, respectively. There was no significant improvement when compared to the 1995-1999 period for any of these groups and patient survival had declined by 1% among recipients of living or standard criteria deceased donors. recipients of living or standard criteria deceased donor kidneys had a 6-7% higher 5-year survival rate and longer graft half-lives than recipients of HLA mismatched kidneys. The number of local HLA-DR matched transplants (excluding zero-HLA-ABDR mismatched grafts) has been declining since 1998 and was affected by the activity of the local donation service area (presumably reflecting the size of the waiting list). There was a modest increase in the percentage of broadly sensitized recipients transplanted during 2002-2004 from 8-10% of standard deceased donor The median age for recipients of primary standard criteria deceased donor transplants increased from 43 during the period 1990-1994 to 51 during 2000-2004 and may explain the lack of improvement in long-term graft survival rates. When patients aged 19-35 were analyzed separately during the 3 periods, there was a 3-4% increase in actuarial or projected 10-year graft survival for recipients of living or younger deceased donor kidneys during each interval (p < 0.001). Changes to the kidney allocation algorithm that affect the role of HLA matching have not had a striking impact on the number or percentage of zero HLA-ABDR mismatched SCD transplants, which account for 16-17% of SCD transplants each year. The number and percentage of HLA-matched ECD transplants declined from 113 (12%) in 2001 to 63 (4%) in 2004. The 56% 5-year graft survival rate for recipients of HLA-matched ECD kidneys was not significantly better than that for HLA-mismatched grafts, whereas HLA-matched and from 2-4% of living donor kidney recipients that was temporally associated with improved technologies for detecting anti-HLA antibodies. The presence of panel reactive antibodies had almost no effect on 5-year graft survival among retransplanted patients. The number of transplants between spouses leveled off in 2001 at about 700 transplants each year. The number of non-spouse unrelated living donor transplants has increased 10-fold over the past 10 years to 1,341 in 2004 and does not appear to be slowing.
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PMID:The OPTN/UNOS Renal Transplant Registry. 1742 21

Sickle cell disease (SCD) is a chronic inflammatory disease associated with multiple organ damage, chronic anemia, and infections. SCD patients have a high rate of alloimmunization against red blood cells (RBCs) following transfusion and may develop autoimmune diseases. Studies in mouse models have suggested that regulatory T cells (Treg) play a role in alloimmunization against RBC antigens. We characterized the phenotype and function of the Treg cell population in a homogeneous cohort of transfused SCD patients. We found that the distribution of Treg subpopulations differed significantly between SCD patients and healthy blood donors. SCD patients have a particular Treg phenotype, with strong CTLA-4 and CD39 expression and weak HLA-DR and CCR7 expression. Finally, we show that this particular phenotype is related to SCD rather than alloimmunization status. Indeed, we observed no difference in Treg phenotype or function in vitro using autologous feeder cells between strong and weak responders to alloimmunization.
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PMID:Partial dysfunction of Treg activation in sickle cell disease. 2477 34

People with sickle cell disease (SCD) are reported to have low rates of HIV infection, slower progression to AIDS and lower HIV-associated mortality compared to the general population. Mechanisms of potential resistance to HIV in SCD are incompletely understood. We retrospectively reviewed the Transfusion Safety Study to compare HIV status between people with SCD and other congenital anemias who were routinely exposed to blood products during the high-risk period before HIV screening implementation. Non-SCD congenital anemia diagnosis was associated with a higher risk of HIV acquisition compared to SCD (OR 13.1 95%CI 1.6-108.9). In addition, we prospectively enrolled 30 SCD cases and 30 non-SCD controls to investigate potential mechanisms of resistance to HIV in SCD. CCR5 and CCR7 expression was lower and CD4 expression was higher on CD4+ T cells from SCD cases compared to controls. Surface expression of CD4+ T cell CXCR4, CD38 and HLA-DR did not differ between the groups. SCD CD4+ T cells were not less susceptible to HIV infection than controls. Levels of multiple cytokines were elevated in the SCD plasma, but SCD plasma compared to control plasma did not inhibit HIV infection of target cells. In conclusion, our epidemiological data support people with SCD being resistant to HIV infection. Potential mechanisms include lower CD4+ T cell expression of CCR5 and CCR7, balanced by increased CD4 expression and cytokine levels, which did not result in in vitro resistance to HIV infection. Further study is needed to define the risk and pathophysiology of HIV in persons with SCD.
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PMID:Influence of sickle cell disease on susceptibility to HIV infection. 3226 41