CHEMICAL CHARACTERIZATION OF GLYCOPEPTIDES FROM HUMAN gammaM-GLOBULINS.

A survey of human pathological macroglobulins revealed that gammaM can be divided into at least two groups on the basis of carbohydrate composition. Differences between the two groups exist in the total percentage of carbohydrate (10.69 +/- 1.49% for group 1, 7.71 +/- 0.65% for group II) which is attributable to variation in hexose content. Glycopeptides from macroglobulins of each group were purified from pronase digests and characterized chemically. Macroglobulins from each group contain three types of oligosaccharides. Glycopeptide I for each group consisted of mannose, galactose, and NAG with a ratio of 3:2:1 for group I and a ratio of 2:1:2 for group II. Glycopeptide II consisted of mannose, galactose, and NAG (9:1:2) for group I, and mannose, fucose, galactose, and NAG (2:1:3:2) for group II. Glycopeptide III in both groups consisted of mannose, fucose, galactose, NAG, and sialic acid with a ratio of 6:2.5:2.5:5.5:2 for group I and a ratio of 5:1:1:6:1 for group II. Molecular weight estimations by gel filtration indicates that there are 10 glycopeptides I and II and 20 units of glycopeptide III per molecule of gammaM.

Characteristics of streptococcal group-specific antibody isolated from hyperimmune rabbits.

Intravenous immunization of New Zealand red rabbits with streptococcal group-specific bacterial vaccines yielded sera which possessed markedly elevated gamma-globulin. The sera of one rabbit immunized with Group A-variant vaccine possessed 55 mg/ml of gamma-globulin. The bulk of this gamma-globulin, identified as gamma(G)-globulin, was homogeneous by zone electrophoresis and of specificity directed against the Group A-variant carbohydrate antigen. L chains isolated from specific antibody obtained from an immune precipitate were distributed as a single band on starch gel electrophoresis, whereas the normal gamma-globulin traveled as a diffuse smear. These data suggest that the rabbit streptococcal Group A-variant antibodies possess a limited range of physicochemical properties and electrophoretic mobility compared to that generally observed for the normal complement of gamma-globulin.

Biological properties of myeloma proteins.

The paraproteins frequently cause major symptoms in patients with plasma cell dyscrasias. This may be due to their quantity in the circulation, to some unusual physicochemical property, or to a biological effect resulting in interaction with other serum proteins. Detection of antibody-combining activity in myeloma proteins has led to important new information on combining-site structure and the kinetics of antigen-antibody-combining activity. Some antibody-combining specificities seem to be present in a higher than expected frequency. As yet, no major therapeutic advances have followed this more precise characterization of the paraprotein, though some interesting possibilities have been explored in animal models.

Jaccoud arthritis.

Jaccoud polyarthritis is thought to be a rare complication of rheumatic fever. It is characterized by severe rheumatic fever, with repetitive or prolonged attacks, associated with a painless, but deforming arthritis affecting the small joints of hand and feet. Radiologically, erosion of the metacarpal heads may be present. All described cases have shown obvious rheumatic heart disease. Two patients had the clinical and radiographic features of Jaccoud arthropathy who had no antecedent history of rheumatic fever. Jaccoud arthropathy may have diverse causes.

Specific IgE antibody responses to ragweed allergens Ra5S and Ra5G associated with distinct HLA-DR beta genes.

Previous studies have established that sensitivity (IgE antibody response) to Ra5S, a 5000 mol. wt protein of short ragweed pollen, is significantly associated with host possession of HLA-DR2. The same allele was implicated [Goodfriend et al. (1985) Molec. Immun. 22, 899-906] in sensitivity to Ra5G, a 4400 mol. wt homologue of Ra5S in giant ragweed pollen, based on frequency of co-sensitivity to both proteins. However, data reported here generated in HLA-DR assays of mono-sensitive individuals demonstrate that sensitivity to Ra5S and Ra5G is associated with separate alleles: DR2 and DRw52 respectively. Results consistent with the same sensitivity/DR associations were obtained in immunoabsorption studies with sera from co-sensitive individuals. As HLA-DR2 and DRw52 have identical alpha but different beta chain types (beta 1 and beta 3), it was considered that IgE antibody responses to Ra5S and Ra5G are associated with distinct DR-beta genes.

Ra5G, a homologue of Ra5 in giant ragweed pollen: isolation, HLA-DR-associated activity and amino acid sequence.

Recent studies [Marsh et al. (1982) J. exp. Med. 155, 1439-1451; Coulter (1983) M.Sc. thesis, McGill University, Montreal, Canada; Coulter et al. (1983) in Genetic and Environmental Factors in Clinical Allergy (Edited by Marsh D.G., Blumenthal M.N. and Santilli J., Jr), University of Minnesota Press, Minneapolis, MN] have shown a highly significant association between HLA-Dw2/DR2 and host sensitivity to the 5000-D, 4-disulfide bonded protein Ra5S of short ragweed pollen. To extend these findings, we isolated Ra5G, an Ra5S-like protein, from giant ragweed pollen by gel and ion-exchange chromatography. The protein was homogeneous by polyacrylamide gel electrophoresis (pH 4.3), reverse-phase high-performance liquid chromatography, and antigenic assays. Its mol. wt and amino acid composition (including 8 half-cystine residues) were closely similar to Ra5S, but the two proteins had little or no antigenic or allergenic cross-reactivity. In a study of 200 ragweed-sensitive individuals, host sensitivity simultaneously to Ra5G and Ra5S was significantly associated with the DR2 allele. The amino acid sequence of Ra5G was determined and showed close homology with Ra5S. The potential function of a highly homologous decapeptidyl sequence stretch is discussed in relation to Ir gene control of immune response to the 2 proteins.

Cerebellar degeneration with Hodgkin disease. An immunological study.

A 21-year-old woman with subacute cerebellar degeneration was found to have Hodgkin lymphoma. Radiation therapy for the lymphoma halted the progression of her neurological disease. Using an immunofluorescent technique, we found the patient's serum to have antibodies to cerebellar Purkinje cells.

Transient monoclonal proteins in drug hypersensitivity reactions.

Two patients were studied in whom monoclonal (M) immunoglobulin G (IgG) proteins developed during the course of a serum sickness-like drug hypersensitivity reaction to cloxacillin (Orbenin) and sodium cephalothin (Keflin), respectively. The clinical evidence and time sequence of events support this association. In both patients there was evidence of an active antibody response to the given antibiotic and to the benzylpenicilloyl group as well. However, protein fractions obtained by agar gel preparative electrophoresis failed to show a higher antibody concentration where the M peak was located, and absorption experiments performed with penicillin G-, cloxacillin- and cephalothin-coated red cells failed to absorb these M proteins. These transient paraproteins can be seen in association with antibiotic(s) administration in the context of a hypersensitivity reaction and do not apparently represent a specific immune response.

Evidence for a cutaneous secretory immune system in rainbow trout (Salmo gairdneri).

Serum and mucus of untreated rainbow trout did not contain detectable agglutinating antibody to sheep red blood cells. Intraperitoneal injections of sheep erythrocytes resulted in production of specific antibody in both serum and mucus. Immuno-diffusion and absorption studies confirmed that mucus and serum antibodies are antigenically similar. Indirect fluorescent antibody techniques demonstrated the presence of immunoglobulin-containing plasma cells in cutaneous dermis and mucus, supporting the hypothesis that an independent mammalian-like secretory immune system is operative in fish.

Monoclonal gammopathies antigen driven in autoimmune diseases.

An important link exists between cancer, autoimmune diseases and immune deficiency. This presentation will review some data concerning clonal growth in B lymphocytes, with focus on the occurrence of autoantibody f2p4vity in the monoclonal proteins, which are the products of the clonally expanded lymphocyte plasma cell population. The role of antigen in causing or promoting monoclonal B cell growth is considered for several different forms of monoclonal gammopathies benign, malignant, and secondary. There is recent demonstration of M-proteins and clonal growth complicating HIV infections and some autoimmune conditions which illustrate well the link between cancer, autoimmunity and immune deficiency.

The frequency of Leu 1+B cells in autoantibody positive and negative autoimmune diseases and in neonatal cord blood.

There is increasing evidence supporting the involvement of Leu 1+B cells in the development of human autoimmune diseases. In this study, the frequency of Leu 1+B cells has been analysed by a multiparameter FACS machine in newborn cord blood, and in the peripheral blood of several autoimmune patients and their healthy adult controls. Higher frequencies were observed in systemic lupus erythematosus (SLE), in seropositive rheumatoid arthritis (RA) and in newborn cord blood compared to control adults and seronegative RA. No relationship was observed between the frequency of Leu 1+B cells, and the age, sex and medication of the subjects.

Cold insoluble globulin: relationship with lymphocytotoxins in autoimmune diseases.

Lymphocytotoxic activity is known to better occur at low temperatures and to be relatively enriched in cryoglobulins. As the cold insoluble globulin, Fibronectin, is a main component of cryoglobulins, experiments were carried out to find out whether Fibronectin was involved in the mechanism of cytotoxicity or not. No direct or indirect (complement-mediated) effects were seen. A significant association was observed between lymphocytotoxic activity and circulating immune complexes and between Fibronectin positivity and cytotoxicity in PEG-precipitates of sera from three groups of patients affected with SLE, RA and Ps.A. respectively. As Fibronectin is a cryoprecipitagogue protein, possible implications of these findings are discussed.

Asplenia in systemic lupus erythematosus: a simple coincidence?

Two patients with asplenia and systemic lupus erythematosus are described. Both patients presented with unusual symptoms of the disease. The possible association of asplenia, presumably congenital, and systemic lupus erythematosus is discussed.

Expression of c-myc protein in skin and synovium in psoriasis and psoriatic arthritis.

Monoclonal antibody against c-myc protein was used in the avidin-biotin-peroxidase complex procedure to examine frozen sections of psoriatic and normal skin and psoriatic synovium for the presence of c-myc protein. A significantly greater percentage (88%) of epithelial cells from psoriatic skin lesions stained for c-myc than uninvolved skin (62%) from both psoriatics and normals (p less than 0.001). The intensity of the stain appeared weaker in normal skin specimens. Greater than 95% of psoriatic hyperplastic synovial lining cells stained strongly for c-myc. In all cases, the c-myc staining was confined to the nuclei with no evidence of cytoplasmic staining.

Measurements of red blood cell methotrexate concentrations and lymphocyte subsets during therapy of rheumatoid arthritis.

Nine patients with rheumatoid arthritis were treated with low dose oral weekly methotrexate for 6 months. Successful therapy was not associated with changes in concentrations of total circulating lymphocytes nor with alterations of T lymphocytes in the helper-inducer, OKT4, or cytotoxic-suppressor, OKT8, subpopulations. Concentrations of methotrexate in circulating erythrocytes stabilized by 1 month of therapy and this measurement did not correlate with clinical efficacy or methotrexate toxicity in the long-term patient assessments.

Epilepsy etiology with special emphasis on immune dysfunction and neurovirology.

The etiology of epilepsy remains in most cases an enigma. Based on the finding of a genetically dependent immune dysfunction in focal epilepsies, brain specimens from 16 patients, ranging in age from 6 to 39 years and operated on for therapy-resistant focal, mainly temporal lobe epilepsy were analyzed for the presence of viral DNA. The PCR technique was used for detection of viral DNA from the herpes virus group. HSV-1 was found in 44% CMV in 50%, and HHV-6 in 25%. Three patients were positive for more than one of these viruses. The control material, consisting of only 4 brain tissue samples, showed DNA from HSV-1 in one case. Until more brain samples from controls have been examined, caution must be taken before a viral etiology is applied to focal epilepsy.

Asplenism and systemic lupus erythematosus.

Although functional hyposplenism, secondary to Fc-receptor blockage by circulating immune complexes saturation, has been described in systemic lupus erythematosus (SLE), only few cases of complete asplenism have been reported. We observed a 60-year-old woman with congenital asplenism who presented with active SLE. The course and the clinical characteristics of such patients are reviewed and the relationship between the asplenic state and initiation and severity of SLE are discussed. These patients are at high risk for fatal pneumococcemia and pneumococcal vaccine is recommended even if long term results are still conflicting.

Association and linkage between alcoholism and eleven serological markers.

Sera from alcoholics and their nonalcoholic first-degree relatives were analyzed for 11 serological markers. A lower prevalence of the S antigen in the nonalcoholic relatives and linkage in repulsion between the D gene of the Rh system and alcoholism were found. All the alcoholics and the relatives had an SS phenotype, when analyzed for complement C3, compared with a prevalence rate of about 50% in other studies. The first two associations involve blood groups, the latter a serum protein.