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Biomedical subjects

D P Sengar

Publications and source records attributed to D P Sengar.

At least 19 recordsLinked to original sources
PubMed1998

A novel DRB3 allele (DRB3*0208), a new allelic variant of DRB1*1502 (DRB1*15023) and two new DQB1 (DQB1*03012 and DQB1*0614) alleles.

Four novel HLA Class II alleles were identified using CANTYPE reverse hybridization assay. The initial unusual SSO hybridization patterns were confirmed by cloning and sequencing analysis. DRB3*0208 allele is identical to DRB3*0202 except for three nucleotide substitutions (GAT-->AGC) changing codon 57 from Asp to Ser. This polymorphism has so far been undetected in DRB3 alleles. DRB1*15023 differs from DRB1*15021 by a single silent nucleotide substitution (AAC-->AAT, both encoding for Asn) at codon 33. This polymorphism has not, until now, been identified in DRB alleles. Compared with DQB1*03011, the novel DQB1*03012 contains a single silent nucleotide substitution (GCA-->GCG, both encoding for Ala) at codon 38. Finally, DQB1*0614 allele is identical to DQB1*0603 except for a single nucleotide substitution (TAC-->TTC), changing codon 9 from Tyr to Phe. Polymorphisms observed here in the DQB1*03012 and DQB1*0614 alleles are present in several of the known DQB1 alleles. DRB3*0208, DQB1*03012 and DQB1*0614 may have arisen from gene conversion, but the DRB1*15023 most likely was generated by a point mutation event. DQB1*0614 was detected in three related subjects, while each of the other three new alleles has only been detected once.

Alleles↗
PubMed1996

MHC studies of the primary antiphospholipid antibody syndrome and of antiphospholipid antibodies in systemic lupus erythematosus.

OBJECTIVE: To study the association of HLA Class I, II, and III alleles with antiphospholipid antibodies, both in patients with systemic lupus erythematosus (SLE) and patients with primary antiphospholipid antibody syndrome (APS). METHODS: We studied Caucasian patients with SLE (n = 91) and with primary APS (n = 16) followed at the Ottawa General Hospital Rheumatic Disease Unit. Antiphospholipid antibodies (aPL) were defined by a positive IgG anticardiolipin antibody by serum ELISA and/or the presence of a lupus anticoagulant. HLA Class I by serology and Class II by restriction fragment length polymorphism were compared in patients with and without serum aPL, and in patients with primary APS compared to controls. C4A null alleles were studied in patients with primary APS. RESULTS: aPL were found in 19 of 91 (21%) patients with SLE, and were associated with deep venous thrombosis in this group. In patients with primary APS, stroke, deep vein thrombosis, and recurrent fetal loss were the most common clinical features. HLA-DR17(3) and Dw24 were decreased in patients with SLE with aPL and in patients with primary APS. HLA-DR4 and the linked DR53 were significantly increased in patients with primary APS compared to patients with SLE. In patients with aPL (SLE and primary APS) compared to patients with SLE without aPL, associations were found with HLA-DR53 (p = 1.5 x 10(-4), RR 5.1), DR7 (p = 0.01, RR 5.6), and to a slightly lesser degree DQ7 (p = 0.005, RR 3.6). C4A null alleles by protein allotyping and the C4A gene deletion were not associated with primary APS. CONCLUSION: We confirm the association of aPL with HLA Class II alleles. The strongest association with aPL in our study is with the HLA-DR53 haplotypes, some of which include the DQ7 allele, as suggested in an earlier study. The HLA-B8, DR17, DQ2 haplotype so closely associated with SLE is significantly decreased in both patients with aPL and with primary APS. C4A null alleles are not associated with primary APS in this population. Our study suggests the aPL response in SLE and primary APS is immunogenetically distinct from SLE itself.

Alleles↗
PubMed1995

Comprehensive typing of HLA-DPB1 alleles by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Comprehensive typing of 53 HLA-DPB1 alleles was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using 78 polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) defined DNA specimens (14 retrospective, 64 prospective). A single primer pair was used to amplify the second exon to obtain DPB1-specific amplified product of 294 bp. A combination of RFLPs and cleaved/uncleaved patterns of various endonucleases was employed to resolve DPB1 alleles. A panel of 13 endonucleases (RsaI, Sau96I, BsrBI, DdeI, BsaJI, BssHII, ScaI, ScaI, BbvI, BsgI, FokI, Bsp1286I and BstUI) yielded unique RFLP patterns for all but 2 pairs of DPB1 alleles. However, these remaining 2 pairs of rare alleles could be resolved by an additional digestion with AciI (DPB1*3901 from 4001 and DPB1*4901 from 5301). The unique RFLP patterns of 21 DPB1 alleles using PCR-SSOP typed DNA specimens had been verified. Of the 1,378 possible heterozygotic patterns, 69 pairs and a triplet had been identified that would yield identical RFLP patterns. However, all but one pair, DPB1*3901/5301 from 4001/4901, of these heterozygotes could be resolved by double digestions with appropriately selected endonucleases from the panel used here. Thus, PCR-RFLP remains a simple and effective method for high resolution DPB1 typing.

Alleles↗
PubMed1994

Comprehensive typing of DQB1 alleles by PCR-RFLP.

The protocols represented in this report can resolve all 22 DQB1 alleles. The second exon of DQB1 was subjected to PCR using two group-specific primers to obtain DQB1 group 1 (DQ5 and DQ6) and group 2 (DQ2, DQ3, DQ4) specific amplified products, respectively. Three endonucleases, ApaI, BssHII and NciI, can provide typing of DQ5 and DQ6 based on easy-to-read uncleaved, cleaved and a combination of uncleaved/cleaved patterns. Similarly, two endonucleases, FokI and BgII can define the specificities DQ2, DQ3 and DQ4. Moreover, all 13 group 1 DQB1 alleles and all but one of their 78 possible heterozygotes can be unambiguously resolved using an extended panel of 10 endonucleases. The remaining pair of heterozygotes, DQB1*05031/0603 and 05032/0608, can however be resolved by double digestion with BsmFI and SfaNI. RsaI splits the previously unresolved alleles DQB1*0602 and 0603 in the amplified products of the modified primer SDQ-01. Fnu4HI can resolve DQB1*0606 from 0605. DQB1*0603, 0607 and 0608 can be resolved by SfaNI and the new endonuclease BsmFI. The comprehensive typing of group 2 DQB1 alleles can be achieved using five endonucleases. All 9 group 2 DQB1 alleles and all but one pair (DQB1*0301/0302 from DQB1*03032/0304) of 36 possible heterozygotes can be resolved. Thus, PCR-RFLP remains a simple, inexpensive and reliable method for DQB1 typing. The PCR-RFLP can be used for comprehensive DQB1 typing either independently or to complement the PCR-SSP and PCR-SSOP methods.

Alleles↗
PubMed1994

Comprehensive typing of DR52 (DRB3)-associated DRB1 and DRB3 alleles by PCR-RFLP.

The DR52-associated DRB1 and DRB3 alleles were resolved by PCR-RFLP. Second exon was amplified using four primer pairs (groups 1-4) for DRB1 and a pair for DRB3 alleles. Except for three endonucleases, all others had either none or only one site for a specific amplified product. Group 1 primers amplify 10 DRB1 alleles (DRB1*0302, 1101, 1302, 1303, 1305, 1307, 1402, 1403, 1407 and 1409). All but one pair, DRB1*1402 from 1409, could be resolved using seven endonucleases (ApaI, SacII, FokI, AvaII, BsaAI, BsrBI and SfaNI). Group 2 consisted of four alleles (DRB1*1201, 1202, 1404 and 1411) that can be resolved along with co-amplified DRB1*0804 and 0806 using five endonucleases (AvaII, SacII, FokI, HaeII and RsaI). Group 3 primers amplify 15 DRB1 alleles (DRB1*0301, 0303, 1102, 1103, 1104, 1107, 1301, 1304, 1306, 1308, 1401, 1405, 1406, 1408 and 14-New), which can be resolved using nine enzymes (KpnI, AvaII, FokI, SacII, HaeII, BsrBI, SfaNI, DdeI and RsaI). BsrBI, a new endonuclease, can resolve DRB1*1301 from 1306 and the previously unresolved allele DRB1*1103 from 1104. DRB1*1410, co-amplified with DR4 group-specific primers, is resolved with PstI which cleaves all DR4 alleles but not DRB1*1410. All four DRB3 alleles (DRB3*0101, 0201, 0202 and 0301) and their heterozygotes are resolved using two endonucleases, RsaI and HphI. Thirty-four DR52-associated alleles and their heterozygotes can be unambiguously resolved, except for DRB1*1402 from 1409.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1993

Comparative studies of the major histocompatibility complex in French Canadian and non-French Canadian Caucasians with systemic lupus erythematosus.

OBJECTIVE: To investigate and compare the predisposing role of major histocompatibility complex (MHC) genes in systemic lupus erythematosus (SLE) in French Canadian and non-French Canadian (mainly Anglo-Saxon descent) Caucasian subjects. METHODS: HLA-A, B, C (serology), DR, and DQ (restriction fragment length polymorphism [RFLP] typing) were determined. RFLP defining a large C4A,21-OHA deletion (Taq I C4) and an Nco I tumor necrosis factor alpha (TNF alpha) RFLP were analyzed in 91 Caucasian Canadians and 91 ethnically matched control subjects. RESULTS: In the total SLE and non-French Canadian SLE populations, HLA-B8, DR3(DR17), Dw24, DQ2, and the C4A gene deletion were associated with SLE. These HLA specificities and the C4A gene deletion were not significantly increased in French Canadian SLE patients compared with ethnically matched controls. When present in French Canadians, the C4A gene deletion was less closely associated with HLA-DR3(DR17), Dw24, DQ2 than in other Caucasians. HLA-DQ6 was associated with SLE in French Canadians. No association of the 2-allele Nco I TNF alpha RFLP with SLE was found in this population, in either ethnic group. CONCLUSION: These results support the importance of ethnic background in the study of MHC genes and SLE. The extended HLA-B8,DR3,C4A null haplotype is found mainly in SLE patients of Anglo-Saxon descent, while the DQ6 specificity is associated with SLE in French Canadians. This relatively genetically homogeneous Caucasian population offers the opportunity to study non-HLA-B8,DR3-linked MHC influence in SLE.

Canada↗
PubMed1993

Early-onset autoimmune hepatitis is associated with a C4A gene deletion.

BACKGROUND: Autoimmune hepatitis is an immunologically mediated disorder with some similarities to systemic lupus erythematosus, including an association with HLA-A1, B8, DR3. This haplotype includes a C4A, 21-OHA gene deletion. Low serum levels of complement and C4 null alleles have been reported in autoimmune hepatitis, but studies have been at the protein level only. METHODS: Twenty-four white patients with autoimmune hepatitis were studied by Southern blots using a C4A gene complementary DNA probe. HLA A, B, and C typing was determined using standard microcytotoxicity assays, and DR and DQ specificities were determined by restriction fragment length polymorphism analysis. RESULTS: Thirteen of 24 patients had the C4A gene deletion compared with 12 of 90 controls. HLA-A1 and B8 were increased in patients with autoimmune hepatitis, as were HLA-DR3 (DR17), Dw24, DQ2. Patients with a C4A gene deletion presented at a younger age than those without the deletion and had significantly lower serum C3 and C4 levels. The C4A gene deletion was associated with HLA-A1, B8, DR3 in all but 1 patient who was HLA-DR3 negative. CONCLUSIONS: A C4A gene deletion is found in patients with autoimmune hepatitis, especially those presenting at a young age. This complement gene deletion may be an important factor in the development of this disease.

Adolescent↗
PubMed1991

A rare complement component C4 restriction fragment length polymorphism in two families with systemic lupus erythematosus.

C4 null alleles with or without C4A,21-OHA gene deletions are associated with systemic lupus erythematosus (SLE) in various populations. We describe a new, rare C4 restriction fragment length polymorphism (RFLP), a Taq I 3.5 kb fragment, in 2 patients with SLE and their families. This RFLP is not associated with one particular major histocompatibility complex (MHC) haplotype and has not been reported in patients with SLE, patients with congenital adrenal insufficiency, or in healthy individuals.

Adult↗
PubMed1991

The importance of class I and class II HLA in cadaveric renal transplantation.

The importance of avoiding mismatches (MM) at Class I and Class II HLA antigens in cyclosporine-treated renal allograft patients is controversial. In order to assess the role of HLA, 200 consecutive cadaveric renal allografts over a 4-year period were analysed. All patients received cyclosporine/predinisone immunosuppression and 75% were induced with ALG. Minimum follow-up period was one year. HLA A, B, DR, DQ, and DRw52/53 typing were available on 77-100% of allografts. A beneficial effect was noted at the HLA A locus. One-year survival was 87.2% in the 0 and 1 HLA A MM group combined vs 73.8% in the 2 HLA A MM group (p less than 0.05). The mean creatinine level at one year was also lower in the 0 plus 1 MM vs 2 MM group: 152.8 mumol/L vs 184.8 mumol/L, respectively (p less than 0.05). Significantly fewer rejection episodes occurred in the 0 and 1 HLA DQ MM group combined vs the 2 MM group. Steroid-resistant rejection episodes (SRRE) were not associated with the number of HLA MM. Patients who had an SRRE had significantly higher mean current and historical peak panel reactive antibodies (PRA) than patients who did not have SRRE. These results indicate that avoiding mismatches at the HLA A locus may improve renal allograft survival, and matching at HLA DQ may predispose patients to a more quiescent post-transplant course. The degree of preoperative sensitization may be an important etiologic factor in SRRE.

Cadaver↗
PubMed1989

Role of class II HLA in cadaveric renal transplantation: a recent update.

Class II HLA matching, especially HLA-DQ and DR, significantly improved allograft survival. HLA-DQ and DR matching may also be associated, in general, with a quiescent posttransplantation course, reduced incidence of SRRE, and somewhat better response to OKT3 rescue therapy. We conclude that the matching of class II HLA remains an important predictor of transplant outcome in CyA-treated patients and should form the primary basis of organ sharing.

Adolescent↗
PubMed1989

Long-term patient and renal allograft survival in HBsAg infection: a recent update.

Although the risk of HBsAg infection has now been reduced significantly by screening of blood, isolation of HBsAg+ patients, and more recently by vaccination, transplant-eligible patients can still be seen. We observed an increased mortality in HBsAg+ patients during 5 to 10 years posttransplantation. However, this could not be attributed to liver disease or dysfunction. Increased mortality and morbidity due to liver disease or dysfunction 10 years posttransplantation suggest that the HBsAg+ patients remain at a higher risk for developing liver disease during that period. In our study, HBsAg+ patients had a 10-year posttransplantation period relatively free of serious liver disease or dysfunction. Furthermore, both HBsAg+ and HBsAg- patients had a similar long-term allograft survival. It is unknown how the use of cyclosporine will affect those survival statistics. We, therefore, believe that HBsAg positivity per se should not constitute an absolute contraindication to transplantation.

Adolescent↗
PubMed1987

Role of class I and class II HLA antigens in cadaveric renal transplantation.

HLA matching at MT and DQ appears to be an important predictor of allograft survival. Allografts with no MM at MT and DQ have a good outcome while a known MM at MT and DQ appears to be associated with poor allograft outcome. Thus, our priority should be to avoid an MM for these broad-reacting specificities and then to minimize incompatibilities at DR and HLA-B. Furthermore, our data indicate that allografts with MM at DQ and two MMs at HLA-B appear to be at a higher risk. Perhaps these latter transplants should not be performed with conventional immunosuppressive therapy.

Cadaver↗
PubMed1984

Frequency of HLA antigens in patients with psoriasis or psoriatic arthritis.

A study of 138 patients with psoriasis--74 with psoriasis alone and 64 with psoriatic arthritis--revealed a significantly increased frequency of the HLA antigens A1, A28, B13, DR7 and MT3 in those with psoriasis alone and of Bw39 in those with psoriatic arthritis. The frequency of B17 was higher in both patient groups than in a control group of healthy individuals. The frequency of DRw6 was slightly higher in the patients with psoriasis alone (17.8%) than in the controls (4.7%), and that of DR7 was higher in the patients with psoriatic arthritis (52.9%) than in the controls (32.6%). Elevated levels of serum IgG and IgA along with positive results of tests for antinuclear antibody or rheumatoid factor or both were present in less than a tenth of the patients with psoriatic rash alone and in up to a third of those with psoriatic arthritis. Psoriatic arthritis was found to be less likely to develop in patients with purely guttate psoriasis than in those with other types of psoriasis. Clinical subtypes of psoriatic rash or psoriatic arthritis were not associated with the presence of particular HLA antigens.

Adult↗