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N K Mehra

Publications and source records attributed to N K Mehra.

At least 73 records · Page 4Linked to original sources
PubMed1994

Restriction fragment length polymorphisms in HLA-DR4-DQ3 haplotypes associated with rheumatoid arthritis.

Restriction fragment length polymorphism (RFLP) patterns were studied in serologically confirmed DR4-DQ3 positive patients with rheumatoid arthritis by Southern blot analysis using full length cDNA probes specific for DRB, DQA and DQB hybridized with genomic DNA digested with informative restriction endonucleases. The RFLP patterns correlated with serology confirming all patients to be DR4+ve. The DQB1*0302 (DQ8) allele identified by 12.0kb BamHI, 3.3kb Hind III and 1.8kb Taql fragments was present in all patients suggesting them to be DR4-DQB1*0302. Hybridization of Taq 1 and PVU II digested genomic DNA with DQA cDNA probe revealed four informative RFLP patterns. While three of them correlated with known DR4 subtypes, one was a new polymorphism observed specifically in Indian patients with rheumatoid arthritis. The study further indicated that two of the several known subtypes of DR4, viz., DRB1*0401-DW4-DQB1*0302 and DRB1*0404-DW14-DQB1*0302 may be implicated in susceptibility to rheumatoid arthritis in the Indian population.

Arthritis, Rheumatoid↗
PubMed1993

HLA-linked susceptibility to rheumatoid arthritis. A study of forty-one multicase families from northern India.

OBJECTIVE: To analyze segregation of rheumatoid arthritis (RA) with HLA-DR4 and/or other alleles in multicase RA families and to compare the segregation patterns among affected and unaffected sibs. METHODS: Forty-one multicase families (22 multiplex and 19 simplex) of northern Indian origin were studied for HLA haplotype segregation. RESULTS: HLA haplotype sharing among affected sibs was observed more often than expected in families in which both parents were healthy (P < 0.05). RA cosegregated with a DR4 haplotype among offspring only in multiplex families in which both parents were unaffected (P < 0.05), while in simplex families, the disease segregated with DR4 only when the allele was from the affected DR4-heterozygous parent. In DR4-negative affected sib pairs, DR1, DR6, and DR10 were inherited from healthy parents more often than expected. CONCLUSION: Dissimilar modes of inheritance are seen among multiplex and simplex RA families. The results of segregation analysis are compatible with the hypothesis that an epitope, rather than an individual DR antigen(s), is responsible for increased risk for development of RA.

Adolescent↗
PubMed1993

Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus in northern India.

Fifty-eight patients with systemic lupus erythematosus (SLE) from Northern India were tissue typed for HLA class I and II antigens. The results revealed an appreciable increase of HLA-DR4 (37.5%) among patients compared with controls (17.9%), P < 0.03. Additionally, haplotype B8-DR3 was encountered frequently in the patient group. The findings suggest an important role of MHC genes in influencing susceptibility to SLE.

Adolescent↗
PubMed1993

Occurrence of autoimmune diseases and relationship of autoantibody expression with HLA phenotypes in multicase rheumatoid arthritis families.

Presence of autoimmune diseases and relationship of autoantibody expression with HLA association has been studied in 44 multicase rheumatoid arthritis (RA) families of Asian Indian origin. An increased prevalence of systemic lupus erythematosus (SLE) was observed in relatives (2.3%). Although HLA-DR4 segregated preferentially with seropositivity in general, no difference was observed among seropositive versus seronegative RA. On the other hand, no HLA association was observed with ANF positivity in these families. An increased frequency of DR7 in the ANF negative and RF negative group of RA patients compared to positive groups suggests that it may act as protective element for the development of autoantibodies in RA. An increased occurrence of DR4 in relatives affected with SLE was observed. While RA segregated mostly with HLA-DR4 in these families, autoimmune thyroid disease and insulin dependent diabetes mellitus (IDDM) segregated with HLA-DR3 suggesting the involvement of at least two sets of HLA-linked autoimmunity favouring susceptibility genes in the Indian population.

Adolescent↗
PubMed1993

Dermatoglyphic patterns of patients with rheumatoid arthritis.

Finger tip and palmar dermatoglyphics were studied in 31 patients (22 females and 9 males) with rheumatoid arthritis (RA) and 38 matched controls (20 females and 18 males) from North India. While not many differences were observed in palmar patterns, a low ending of line A was found on both hands of two patients. Finger tip patterns were significantly different in patients compared to controls. No association with any dermatoglyphic feature and HLA antigens was observed.

Arthritis, Rheumatoid↗
PubMed1993

Immunogenetics of familial rheumatoid arthritis: a study of 41 multicase families.

HLA haplotypes were studied in 41 unrelated families from North India with multiple cases of rheumatoid arthritis. Affected sibpairs shared parental HLA haplotypes more often than expected (chi 2 = 13.6) according to Mendelian segregation. Using the method of sibpair ratio, nonrandom segregation of parental haplotypes was observed among affected sibs. HLA-DR4 was observed in 70% of the probands while among DR4 negative probands, DR10 occurred more frequently. However no specific haplotypic association with the disease was observed in these families.

Adult↗
PubMed1992

HLA-DR4-DQw8, but not DR4-DQw7 haplotypes occur in Indian patients with rheumatoid arthritis.

The distribution of HLA class II antigens in the Asian Indian patients with rheumatoid arthritis (RA) was studied in the present investigation. The results demonstrated that DR4 was significantly increased in both northern (chi 2 = 36.9, P less than 0.00001) as well as southern Indian (chi 2 = 17.3, P less than 0.0001) patients. HLA haplotype analysis revealed the presence of B17-DR4 among southern Indians. Amongst northern Indians, four DR4 haplotypes occurred significantly: A1,B17,DR4; A19,B7, DR4; A30,B13,DR4; and A33,B44,DR4. An analysis of TA10 and DQ'Wa' specificities revealed that all the DR4-DQw3 positive northern Indian RA patients were DQw8 as compared to its frequency of 33.3% in controls. A positive association observed between DR4-DQw7 and RA in some western Caucasian populations was not present in this series. A group of three DR4 positive RA patients were found to be DQw3 negative and DQ'Wa' or DQw4 positive. These results indicated that susceptibility to RA may be controlled by genes in the DR locus independent of any DQ associations.

Adult↗
PubMed1992

Protective & risk DR phenotypes in Asian Indian patients with rheumatoid arthritis.

This study of 168 north Indian patients with rheumatoid arthritis (RA) confirms the significant association of susceptibility to RA with DR4 specificity (P less than 0.0001). This association was observed equally in familial as well as sporadic patients. The HLA-DR2 and DR5 alleles were identified to be conferring protection in RA, DR5 being reduced significantly in the non-familial patients only. None of the other DR antigens revealed any association with RA in this population, including the DR4 negative group of patients. An analysis of the DR phenotypes in patients and controls revealed that DR4 in combination with DR1 provided the highest relative risk (71.9) followed by DR4, DR4 (RR = 4.1). These results demonstrate that susceptibility to RA is not due to a single HLA specificity but the effect of a group of related epitopes occurring in common among subtypes of DR4 as well as in some DR1 alleles.

Adolescent↗
PubMed1991

Analysis of HLA-DR2-associated polymorphisms by oligonucleotide hybridization in an Asian Indian population.

Among major histocompatibility complex class II antigens, HLA-DR2 appears to have a much larger degree of polymorphism than usually recognized by routine serology or restriction fragment length polymorphisms. We have utilized oligonucleotide probes to further identify the DR2 specificity and its molecular subtypes on the basis of specific DNA sequences as they occur in a select sample from the Asian Indian population. In addition, oligonucleotide typing of HLA-DQA1 and -DQB1 genes allowed us to determine specific associations of DRB1, DRB5, DQA1, and DQB1 alleles in DR2 individuals. A set of 60 oligonucleotide probes were hybridized to polymerase chain reaction (PCR)-amplified DNA from DR2 homozygous or heterozygous individuals. The most common DR2 subtypes that occurred in this selected population are: DRB1*1501 (60%), DRB1*1502 (33.8%), and DRB1*1602 (6.2%). No example of DRB1*1601 was detected. By combining these results with the allelic variations at DQA1 and DQB1, we were able to detect at least seven different haplotypes, the most common being DRB1*1502-DRB5*0102-DQA1*0103-DQB1*0601 and DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0502. At least five unexpected combinations, not reported among Western Caucasians, were noticed in this sample. Thus oligonucleotide typing is a valuable tool for defining further polymorphisms in the HLA-D region as exemplified by its applications to typing DR2-positive patients with tuberculoid leprosy and pulmonary tuberculosis.

Alleles↗
PubMed1991

Occurrence of lymphocytotoxins in multi-case rheumatoid arthritis families: relation to HLA.

The presence of lymphocytotoxic antibodies (LCA) and their association with HLA haplotypes has been studied in 27 multi-case rheumatoid arthritis (RA) families (13 multiplex and 14 simplex) in Northern India. Of the total 59 RA patients, 69.4% had cytotoxins in their sera as compared with 2.5% of healthy controls. No differences were observed in the frequency of LCA in relation to sex and rheumatoid factor. LCA against B cells were significantly more predominant than those against T cells. Twenty families studied for correlation of HLA with LCA showed greater intensity of reaction with DR4+ haplotypes, particularly in simplex families. Similarly, the frequency of LCA among patients and unaffected parents was greater in simplex compared with multiplex families. Haplotype sharing with the patient was increased in the relatives positive for cytotoxins in these families. An immunogenetic contribution made by the affected parent and a common environmental stimulus may be responsible for the increased production of LCA in multi-case families with RA.

Antilymphocyte Serum↗
PubMed1990

Is solitary rectal ulcer a manifestation of a systemic disease?

In a prospective study of 22 patients with solitary rectal ulcer, we tried to define the features of this condition, especially the associated systemic features, that may give some clues to its etiopathogenesis. In 15 of these patients a single rectal ulcer was found, whereas in seven patients two ulcers were present in each. Of the total 29 ulcers in these patients, 19 were located on the anterior or anterolateral wall of the rectum and 10 were on the posterior or posterolateral wall. The sigmoidoscopic appearance of the ulcer was quite characteristic, yet a biopsy was considered essential to rule out other pathologic processes. Histological features of the solitary rectal ulcer comprised fibrous obliteration of the lamina propria with disorientation of the muscularis mucosa and extension of muscle fibers into the lamina propria. Evident rectal prolapse was present in only three patients. Recurrent oral ulcerations occurred in four (18.2%) patients and erythema nodosum in one of them (4.5%). Sacroiliitis was present in six of 19 (31%) patients studied radiologically, and human leukocyte antigen (HLA)-B27 occurred in four of the 20 patients (20%) tested for HLA class I antigens. All the four HLA-B27-positive patients had associated sacroiliitis and showed good response to sulfasalazine. These associations raise the possibility that solitary rectal ulcers may be a part of a systemic disease or of several diseases with varied etiology.

Adolescent↗
PubMed1990

HLA antigens in Asian Indian patients with Graves' disease.

A study of 57 Asian Indian patients with Graves' disease revealed a significant increase in the frequency of HLA-DQW2 (61.4%) as compared to the control population (22.6%) giving a relative risk of 5.4. Less prominent but statistically significant increase in the frequency of HLA-A10 (29.8% patients as opposed to 10.5% controls) and HLA-B8 (28.1% patients as opposed to 8.7% controls) was also observed. Further, patients carrying the phenotypes HLA-A10 and HLA-B8 were more prone to develop the disease at a younger age. Two HLA haplotypes, namely A10-B8 and B8-DR3, were found in significant linkage disequilibrium in our patients with Graves' disease. Patients carrying these haplotypes also had a tendency to develop the disease at an earlier age.

Adolescent↗
PubMed1990

Lymphocytotoxic antibodies in patients with systemic lupus erythematosus & their household contacts.

Twenty patients with systemic lupus erythematosus (SLE) and their 51 household contacts were screened for the presence of lymphocytotoxic antibodies. A high prevalence of lymphocytotoxic antibodies (LCTAB) was observed in the patients (80% against T cells and 100% against B cells). The antibodies carried specificity for HLA-B5/35 and HLA-DR2/DR3. A high prevalence of LCTAB was also observed in contacts (55% LCTAB-T cells, 88% LCTAB-B cells) with no difference being seen between consanguineous and non-consanguineous male or female relatives.

Adult↗
PubMed1989

HLA-DR/DQ antigens and reactivity to B cell alloantigen D8/17 in Indian patients with rheumatic heart disease.

D8/17, a B cell alloantigen, and its occurrence with DR/DQ antigens was examined in 54 patients with rheumatic heart disease and matched North Indian controls. Thirty-four patients (62.9%) carried D8/17 as compared with a frequency of 12.5% in controls (chi 2 by Yates', 18.75; p less than 0.0001). A marginally increased frequency of human leukocyte antigen (HLA)-DR3 (44.2% vs. 28.8%) and a significantly reduced frequency of HLA-DR2 (21.1% vs. 46.6%; p less than 0.005) was observed in patients as compared with controls. However, the most significant positive association was observed with HLA-DQw2 (63.4% in patients and 31.5% in controls; chi 2 by Yates', 9.85; p less than 0.005). The DQw2 association was significant only in the D8/17-positive patients. These observations suggest that the disease susceptibility gene in rheumatic heart disease may be nearer to the HLA-DQ locus than to the HLA-DR.

Antigens, Differentiation, B-Lymphocyte↗