This paper reviews studies previously conducted on the effect of anticancer drugs on immune function in man. It provides new data reporting on the effect of short intensive courses of cytotoxic drug therapy on B-lymphocyte and T-lymphocyte number in cancer patients. Both types of lymphocyte were found in this investigation to be equally sensitive to cytotoxic drugs. The degree of absolute cell number reduction and rate of recovery were similar for T-lymphocytes and B-lymphocytes. Other workers have demonstrated, however, that with prolonged administration of cytotoxic drugs B-lymphocyte number and function are more adversely affected than are T-lymphocyte number and function. Immune function which had been suppressed by continuous programs of chemotherapy for periods of up to 2-3 years will, in certain groups of patients, recover to normal or almost normal levels of function. Short courses of combination drug chemotherapy may be followed by "rebound-overshoot" recovery of immune function. This has been associated with a more favorable clinical course than in situations where it does not occur. Chemotherapy and chemoimmunotherapy programs in clinical oncology ought ideally to be initially evaluated for the effect that they have on immune function. This will permit the development of drug dose and time schedules which allow for recovery of immune function and may possibly lead to augmented antitumor responses.

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 AngloSaxon 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 (Tuq I C4) and an Nco I tumor necrosis factor a (TNFa) 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 TNFa 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,DR3-4inked MHC influence in SLE.

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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.

Uremic patients on hemodialysis for periods in excess of 1 year have a significantly better survival rate for their renal allografts than do similar patients hemodialyzed for less than 1 year. Lymphocytes from the patients of both groups show no difference in response in the mixed leukocyte culture reaction and to nonspecific mitogens such as PHA and PWM. A significant difference between the two groups of patients was observed with regard to their cutaneous delayed hypersensitivity reactions and in their in vitro lymphocyte responses to streptokinase-streptodornase. Patients hemodialyzed over 1 year were anergic to skin test antigens and had a significantly diminished in vitro response to streptokinase-streptodornase. Monitoring of patients for delayed cutaneous hypersensitivity reactions and for in vitro lymphocyte responses to streptokinase-streptodornase may be of some practical value in selecting recipients for renal transplantation.

Histocompatibility typing of a family with 15 members and a history of ureteropelvic junction stenosis and 4 families with 23 members and a history of vesicoureteral reflux revealed that these anomalies of the urinary tract may be hereditary and segregate with histocompatibility haplotype within a family. Thus, a close linkage of childhood reflux and ureteral stenosis with that of the major histocompatibility complex of man is suggested. If confirmed by further family studies it will place the gene(s) for vesicoureteral reflux and ureteral stenosis on the 6th pair of human chromosome and open the possibility of using histocompatibility typing as a marker for these anomalies within a family.