Quantitative studies on tumor enhancement in mice. I. Enhancement of sarcoma I induced by IgM, IgG1, and IgG2.

The concentration of specific alloantibody in purified mouse immunoglobulin preparations was determined. When passively transferred in adequate doses, IgM, IgG1, and IgG2 antibodies all induced tumor enhancement in allogeneic hosts. IgM and IgG2 antibodies in high concentration led to inhibition of tumor growth. IgM and either IgG1 or IgG2 had additive effects on tumor enhancement. IgG1, but not IgG2, suppressed the inhibitory effect of IgM in high concentration.

Electrophoretic mobility and agglutinability of red blood cells: a "new" polymorphism in mice.

A quantitative method has been developed to determine agglutinability of mouse red blood cells. Tests with different inbred strains of mice revealed only two phenotypes. The same inbred strains were tested with the cytopherometer to determine the electrophoretic mobility of the corresponding red cells. Again, two phenotypes were uncovered, and faster mobility was found in the red cells that had higher agglutinability. The genetic control of this character is autosomal and codominant, and segregates independently of H-2 and coat color.

Adult Still's disease: manifestations, disease course, and outcome in 62 patients.

Clinical and laboratory manifestations, disease course, outcome, and HLA associations were studied in an inception cohort of 62 subjects with adult Still's disease (ASD) from 5 Canadian universities. Twenty-eight patients (45%) were female and the median age at disease onset was 24 years. In general, the clinical features observed in our patients were identical to those in other published series. However, significantly higher frequencies of sore throat (92%), weight loss (76%), lymphadenopathy (74%), pleuritis (53%), pneumonitis (27%), and abdominal pain (48%) were noted in our patients compared to those in a recent literature review. Liver involvement with hepatomegaly (44%) or abnormal liver function tests (LFTs) (76%) was common and was responsible for the 2 deaths attributed to Still's disease in our series. Severe liver failure always occurred in conjunction with aspirin or NSAID therapy. Therefore, whether or not aspirin or other NSAIDs are used, we recommend close monitoring of LFTs in patients with ASD, especially early in the disease course. Laboratory manifestations were similar to those already reported. Leukocytosis (greater than or equal to 15,000/mm3) was present in 50 patients (81%), a normochromic, normocytic anemia (hemoglobin less than or equal to 10 g/dl) in 42 (68%), and an elevated ESR in all. The mean follow-up of the 62 patients was 70 months (range, 2-163). Twenty-one patients (34%) had a self-limited disease course, 15 (24%) an intermittent course, and 22 (36%) a chronic disease course. Four patients (6%) died, and 2 of these deaths were attributed to Still's disease. For those patients who experienced a recurrence of ASD, the flares were usually of shorter duration and milder in severity than the initial episode. No initiating factor for disease exacerbation was identified in our patients. Although 22 of 62 patients (36%) had a chronic disease course, 52 (90%) were in ARA Functional Class I, and only 4 and 2 patients were in ARA Functional Class II and III, respectively. Patients with Still's disease had higher scores than the controls on the Pain (P less than 0.01) and Physical Disability (P less than 0.05) subscales of Arthritis Impact Measurement Scales health status questionnaire. Joint radiographs performed at the follow-up evaluation disclosed typical carpometacarpal and intercarpal involvement in 16 of 39 patients. In our series, HLA-B17, B18, B35, and DR2 were significantly associated with ASD. Three significant predictors of an unfavorable outcome, either a chronic disease course or a longer time to clinical remission, were identified.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical and sleep laboratory study of narcoleptic symptoms in multiple sclerosis.

Seventy white patients with a diagnosis of MS and typed for their HLA-A, B, C, and DR were studied. A clinical interview and a questionnaire were used to evaluate the presence of narcoleptic symptoms. The prevalence of sleep attacks, cataplexy, and sleep paralysis was significantly elevated among these patients. However, no difference was seen between DR2 and non-DR2 subjects with regard to the incidence of narcoleptic symptoms. Nine DR2 patients complaining of both sleep attacks and cataplexy were studied in the sleep laboratory for five consecutive naps, but no polygraphic evidence of narcolepsy was found.

Alloimmunization to platelet antigen HPA-1a (PIA1) is strongly associated with both HLA-DRB3*0101 and HLA-DQB1*0201.

Antibodies to the platelet HPA-1a antigen can elicit in the newborn a condition known as neonatal alloimmune thrombocytopenic purpura (NAITP). Previous studies based on RFLP analysis showed that 100% of HPA-1a-negative women who produced anti-HPA-1a antibodies (responders) were HLA-DRw52a (DRB3*0101). However, this specificity could also be found in some HPA-1a-negative women not producing anti-HPA-1a antibodies (nonresponders). We have analyzed in detail by PCR-SSOP the HLA-DR, -DQ, and -DP loci of 36 responders and 10 nonresponders. We found that while the allele DRB3*0101 was present in the vast majority of responders (91%), there were exceptions. Furthermore, the DQB1*0201 allele was found to be present in almost all responders (94%), but again was also found in nonresponders. The risk of alloimmunization to HPA-1a in an HPA-1b homozygous mother significantly increases with the presence of either allele, the odds ratio being 39.7 for DQB1*0201 and 24.9 for DRB3*0101. Sequencing of exon 2 of these two alleles from responders indicated no sequence difference when compared with the consensus sequences. This indicates that they do not represent variants when compared with the same alleles found in some nonresponders.

HLA antigens in narcolepsy and idiopathic central nervous system hypersomnolence.

Several studies have shown familial incidence of narcolepsy and idiopathic central nervous system (CNS) hypersomnia. HLA antigen studies performed in mongoloid and caucasoid narcoleptic patients on the A, B, and C loci have yielded conflicting results. The aim of this study is to document a possible association between the HLA system, including the DR locus and excessive daytime somnolence. Thirty-one narcoleptic patients and 10 idiopathic hypersomniac patients were selected and typed for 54 HLA antigens. A family with narcoleptic members in 3 generations was also studied. HLA-DR2 was found in 100% of narcoleptic patients. The frequency of HLA-A3 and B7, which are in linkage disequilibrium with DR2 was also increased in this group. Idiopathic hypersomniac patients showed an increase of HLA-Cw2, DR5, and B27, three antigens known to be in linkage disequilibrium. In the family study, narcoleptic patients were also HLA-DR2; moreover, 3 subjects, one of whom was narcoleptic, were HLA-DR2 as a result of recombination (i.e., genetic crossing-over). These results locate the hypothetic gene associated with narcolepsy more precisely, and indicate that narcolepsy and idiopathic CNS hypersomnolence are two different entities.

Clinical sub-groups of multiple sclerosis in relation to HLA: DR alleles as possible markers of disease progression.

We have examined the distribution of HLA antigens in 70 multiple sclerosis (MS) patients divided in three groups defined according to clinical criteria: benign MS, severe MS, cerebellar MS. We have found a significant association between severe MS and HLA-DR2, and between benign MS of more than 15 years of evolution and HLA-DR3. We review previous work along the same line and conclude that the association of HLA antigens with "clinical subgroups of MS" could indicate a genetically based heterogeneity of the disease and offer help in establishing a prognosis.

Alloimmune neonatal thrombocytopenia: platelet antibody detection using the indirect immunofluorescence test (IIFT).

Two cases of neonatal alloimmune thrombocytopenia are presented. Using the indirect immunofluorescence test on platelets in suspension, the presence of non-agglutinating platelet specific antibodies with the specificity anti-Zwa could be demonstrated. In both cases diagnosis of alloimmunization was made before delivery of a second child, typing of the family was done and recommendations could be made concerning clinical management. Compatibility testing between the mother's serum and donor platelets (Zwa-negative) was predictable of a normal transfused platelet survival in the newborn.

[A new case of allo-anti-LWab]. / Un nouveau cas d'allo-anti-LWab.

A patient admitted to hospital for hip replacement was found incompatible in pretransfusion testing due to allo-anti-LWab antibody, as well as anti-JKb, anti-E and anti-IH antibodies. The patient had a rare phenotype LW(a-b-ab-). The antibodies were acquired though pregnancy and/or transfusion. This newly discovered anti-LWab allowed us to study and emphasize the relevant serological and transfusional aspects related to incompatibility caused by "public" antibodies in association with other alloantibodies. We attempted to update the LW system in the light of Sistonen and Tippett's recent discoveries. We collected the required compatible units of blood through autologous donations and a Central Canadian Red Cross Registry for rare donors.

An immunogenetic study of older age onset rheumatoid arthritis.

Thirty-two patients with older age onset rheumatoid arthritis (ORA), defined as disease onset after age 60, were selected for HLA typing. The majority (69%) were rheumatoid factor (RF) seronegative. An increase in HLA-DR4, though not statistically significant, was seen in ORA (38% vs 17% normals). This antigen was strongly associated with RF seropositivity (70%, p less than 0.01) and rheumatoid nodules (75%, p less than 0.01) in ORA. We conclude that the immunogenetics of ORA are similar to that described for adult RA in general.

The immune response to the HPA-1a antigen: association with HLA-DRw52a.

Antibodies to the HPA-1a antigen can elicit a condition in the new-born known as neonatal alloimmune thrombocytopenia (NAITP). Retrospective and prospective studies have shown that there is a strong correlation between the presence of HLA-DR3, HLA-DRw52 in the mother and the antibody response to HPA-1a. HLA Class II molecules play an important role in the initiation of the immune response and it has been postulated that HPA-1a antibody production could be determined by the presence of a specific HLA Class II molecule at the surface of the antigen-presenting cell. Thirty-one HPA-1a negative women with HPA-1a antibodies (responders) and nine HPA-1a negative women without HPA-1a antibodies (non-responders) were recruited. They were studied using serological HLA Class I and Class II typing and RFLP analysis with a DR beta probe. We found that all responders had the HLA-DRw52a sub-specificity confirming recently published data. Moreover, two of the nine non-responders were also found to be HLA-DRw52a. These results suggest that the HLA-DRw52a molecule is necessary for HPA-1a antibody responsiveness but not sufficient. The results also indicate that in HPA-1a negative women the absence of HLA-DRw52a is associated with a very low risk of being antibody producers and hence, is associated with a very low risk for NAITP in their new-borns.

Autologous donation error rates in Canada.

BACKGROUND: Although certain transfusion risks are eliminated by the use of autologous blood, clerical errors may still occur. In addition, because of differences in donor selection criteria and donor-patient expectations, the consequences of certain errors may be different in autologous and allogeneic donations. STUDY DESIGN AND METHODS: In January 1996, autologous donation error rates in Canada from 1989 to November 1995 were estimated by 1) a detailed questionnaire sent to hospitals supplied by the Canadian Red Cross, Blood Services, Transfusion Center of Quebec at Montreal autologous donation program (n = 31), 2) a review of that institution's quality assurance non-compliance reports, and 3) a detailed questionnaire sent to other Canadian Red Cross centers with autologous donation programs (n = 16) and hospital-based autologous programs in Canada (n = 3). The total number of autologous donations collected was determined from Canadian Red Cross annual reports and information supplied by hospital-based programs. RESULTS: There were 113 errors reported for 16,873 units collected by the Montreal center (1/149 units) based on collection center and hospital data. The most frequent errors were the late receipt of units for surgery (25% of errors) or the receipt of units in the wrong hospital (23%). Other Canadian programs reported 166 errors for approximately 53,500 units collected (1/322 units). However, this figure was based mainly on collection center, and not hospital, data. The most frequent errors were in labeling (48%) and component preparation (25%). One unit of autologous fresh-frozen plasma was transfused to the wrong recipient. Errors were more frequent if components were produced, if units were drawn in hospitals for interhospital transfer, or it units were shipped between Red Cross centers. CONCLUSION: Errors are not infrequent in autologous donation programs. Autologous transfusion should not be considered as being without risk.

A clinical study of older age rheumatoid arthritis with comparison to a younger onset group.

The clinical features, therapy and course of disease in a group of 34 patients with older age onset rheumatoid arthritis (ORA) defined as disease onset after age 60 are compared with a group of 34 rheumatoid patients whose disease onset began at a younger age (YRA). Onset of rheumatoid arthritis (RA) beyond age 60 is not uncommon as ORA represented 33% of all RA patients seen in our rheumatic disease unit. The ORA patients had a shorter mean disease duration (p less than 0.001) and a tendency to less rheumatoid factor seropositivity (p = 0.06) despite random selection for active disease of less than 10 years' duration. Suppressive therapy was employed less frequently in ORA (p less than 0.01) than in YRA but the use of other therapeutic modalities and the last recorded functional class were similar in the 2 groups. ORA patients did have greater functional incapacity at some point in their disease course (p less than 0.01) as well as a greater frequency of weight loss (p less than 0.001) and other acute systemic features at onset than YRA patients. Seronegative ORA appeared to have a favourable disease course in comparison with seropositive ORA.

Electroblotting and immunohistochemical staining for identification of platelet antibodies.

The Western blot procedure has been adapted for use with a biotinylated antiglobulin reagent and a horseradish peroxidase complex (Vectastain ABC) to determine specific sites of antigen binding and permit discrimination between various types of platelet antibodies. Monospecific anti-PlA1 antisera or sera containing mixtures of multispecific HLA and unidentified platelet specific antibodies were tested with PlA1 phenotyped platelets. Using monospecific anti-PlA1, one intense band with relative molecular weight (Mr) of 88,000 and corresponding to glycoprotein IIIa was seen with the PlA1+ platelets. With mixtures of antibodies, reactions were seen with platelet specific antibodies without interference from the HLA antibodies; with one serum a band of Mr approximately 135,000 was identified with Baka+, but not Baka- platelets, indicating the presence of an anti-Baka in the serum. The location of the Baka antigen corresponded to the area for GP IIb. With another serum, a band of Mr 88,000 was revealed with PlA1- and some PlA1+ platelets suggesting the presence of an anti-PlA2. Two additional bands of Mr 160,000 and 200,000 were present on all preparations including autologous controls, probably due to the presence of non-specific IgG. Thus, immunohistochemical staining is readily adaptable to the Western blot technique, and antibodies to platelet-specific antigens can be easily differentiated from HLA antibodies.

HLA-Bw35 and prognosis in adult Still's disease.

Twenty-five patients with adult Still's disease were studied to determine clinical course and possible HLA associations. Two types of disease evolution were distinguishable clinically: a self-limited remitting disease with or without recurrent cyclic exacerbations was found in 11 patients, and a persistent disease with continuous activity for more than 1 year, generally accompanied by progressive joint disease, was determined in 8. Disease course could not be classified in 6 patients. The antigen frequencies of HLA-Bw35 (40%, P less than 0.05) and Cw4 (44%, P less than 0.05) were increased in adult Still's disease as compared to controls (18% and 20%, respectively). Because HLA-Bw35 was associated with self-limited remitting type disease (P less than 0.02), this antigen may be a favorable prognostic marker in adult Still's disease.