Cold reactive lymphocytotoxic antibodies in pulmonary tuberculosis: correlation with disease activity and HLA.

Cold reactive lymphocytotoxic antibodies (LCA) are more reactive in cold than at 37 degrees C and occur following infection, immunization or vaccination and in various autoimmune diseases. In the present study, LCA activity against T and B-lymphocytes has been investigated in patients with pulmonary tuberculosis (PTB), their various clinical sub-groups and consanguineous relatives. Further, the relevance of HLA factors in LCA activity was analyzed. The sera from 144 PTB patients, 52 family contacts and 52 healthy individuals were tested for presence of LCAs by a modified two-stage NIH microlymphocytotoxicity assay. A significant increase in LCA activity against both T (32.6% vs 5.7%, P < 0.0001) and B (59.7% vs 13.4%, P < 0.0000001) cells was observed in PTB patients as compared to healthy controls. There was no correlation between serum LCA activity and sputum acid-fast bacilli status. However, only B cell LCAs revealed significant increase in parallel to disease advancement as assessed by X-ray chest examination. Further, LCA activity was more pronounced in drug responders than drug failure group of patients. No significant difference in the distribution of HLA class I and class II antigens was observed between LCA positive and LCA negative patients. However, panel cells carrying HLA-A1, -A11 and -DR3 were often found reactive in LCA positive patient sera. In household family contacts, LCAs were significantly increased only against B cells as compared to healthy controls (38.4% vs 13.4%, P < 0.01). This study suggests that Mycobacterium tuberculosis infection/exposure could account for the occurrence of LCAs in pulmonary tuberculosis and the strength of these antibodies is related to disease severity and the extent of lung involvement.

Polymorphism in heat-shock protein 70-1 (HSP70-1) gene promoter region and susceptibility to tuberculoid leprosy and pulmonary tuberculosis in Asian Indians.

Heat shock proteins (HSP) act as immunological target structures either by themselves because of an unusual expression pattern, or they are carrier proteins for immunogenic peptides. A three-allele polymorphism of HSP70-1 promoter region was analysed in random patients with pulmonary tuberculosis (PTB), or with tuberculoid (TT) leprosy and healthy controls from North India. HSP70-1A and HSP70-1C occurred more frequently (> 60%) while HSP70-1B occurred infrequently in this population. Only HSP70-1A allele was significantly increased in TT leprosy as compared to healthy controls (91.8% Vs 71.1%, Pc < 0.03, RR = 4.58). Although a strong association of HLA-DR15 was observed with both of these patient groups in earlier studies, no correlation was found between HSP70-1 promoter alleles with any of the HLA allotypes. Amongst six possible genotype combinations of HSP70-1 promoter allele, only four (A/A, A/B, A/C, C/C) were encountered in Asian Indians. A significant increase of HSP70-1 A/C genotype was observed among DR15 negative PTB patients as compared to DR15 negative controls (87.5% Vs 35.7%, X2 = 8.6, Pc < 0.02) giving highest relative risk of 12.6. These findings suggest that HSP70-1 genes may play a secondary role to HLA-DR in governing susceptibility to mycobacterial infectious diseases.

HLA class I profile in Asian Indian patients with pulmonary tuberculosis.

HLA class I antigen profile was studied in 153 unrelated patients with pulmonary tuberculosis (PTB), 40 family contacts and 289 healthy individuals by the NIH microlymphocytotoxicity test to find out the role of HLA-A, -B, -C alleles in influencing susceptibility to PTB and its various clinical groups. HLA-A2 was found to be significantly increased in the total patient group as compared to controls (38.6% vs 26.3%, p < 0.01, RR = 1.76). The increase of HLA-A2 was more pronounced in the sputum negative patients (59.4%, pc < 0.001, RR = 4.1) suggesting its possible role in the mediation of CD8+ suppressor T cell activity against Mycobacterium tuberculosis, resulting in the development of limited disease in these patients. Further, HLA-B18 was found to be decreased in patients as compared to controls (2.6% vs 7.3%, p < 0.05, RR = 0.34). None of the class I antigens was associated with the dynamics of chemotherapy or disease severity as assessed by the extent of lung involvement on chest X-ray examination.

Dorsolateral prostatic phosphomonoesterases and adenosine triphosphatases in hypo- and hyperthyroid rats.

Specific activities of phosphomonoesterases (acid and alkaline phosphatases) and adenosine triphosphatases (Mg2+, Ca2+ and Na+/K+ dependent ATPases) of dorsolateral prostate were studied in albino rats, under altered thyroid hormone status. Thyroidectomy induced hypothyroidism and thyroxine administered hyperthyroidism (25 micrograms/100 g body wt/day for 60 days, im) showed no impact on the activity of acid phosphatase. Three fold decrease in the activity of alkaline phosphatase was observed in hyperthyroid group. Ca2+ and Mg2+ dependent ATPases were significantly decreased in hypo- and hyperthyroid status whereas Na+/K+ ATPase was decreased in hyperthyroidism and showed an opposite trend in hypothyroid group.

Ventral prostatic phosphomonoesterases and adenosine triphosphatases in hypo- and hyperthyroid albino rats.

Specific activities of prostatic phosphomonoesterases (acid and alkaline phosphatases) and adenosine triphosphatases (Mg2+, Ca2+ and Na+/K+ dependent ATPases) were studied in albino rats, under altered thyroid hormone status. Thyroidectomy induced hypothyroidism decreased the specific activities of acid and alkaline phosphatases, Na+/K+ and Ca2+ dependent ATPases in ventral prostate. Hyperthyroidism (25 micrograms thyroxine/100g body weight/day for 60 days, im) enhanced the activities of acid phosphatase and Na+/K+ dependent ATPase, while Ca2+ dependent ATPase decreased. The altered thyroid status had no effect on the activity of ventral prostatic Mg2+ dependent ATPase. The data obtained in the present study showed differential and specific responses of various ventral prostatic phosphatases to the hypo or hyperthyroid status. The study also shows the necessity of an optimum level of thyroid hormones to maintain the normal activities of these enzymes and their secretory function in ventral prostate.