Search

Flow cytometric analysis of peripheral blood (PB) S + G2/M phase size was performed in 73 adult patients with untreated acute non-lymphoblastic leukaemia, to assess whether the results may correlate to response rate and patient prognosis. All patients were treated with the same induction chemotherapy regimen: ARA-C alone or in combination with an anthracycline antibiotic. Pretreatment PB S + G2/M phase size is significantly correlated to induction response rate (p less than 0.02), duration of response (p less than 0.02) and duration of survival. Patients with low PB S + G2/M phase size experience a longer survival, in patients over and below 50 yr (p less than 0.001). Lastly, early deaths tend to be more frequent in the high median age and high PB S + G2/M phase size group. Our study suggests that PB S + G2/M phase size has prognostic significance in obtaining response and duration of survival.

Objective: To examine the contribution of genetic and environmental factors to disease occurrence in 26 families with two or more members affected with systemic lupus erythematosus (SLE). Methods: Genetic and environmental factors were examined by HLA-A, B, C/DR typing and by determining the presence of lymphocytotoxic antibodies (LCA) in patients and their consanguineous and non-consanguineous relatives. Results: No association between SLE and HLA-A, B, C antigens was found. There was, however, a significant association with HLA-DR2 in white subjects with SLE. The most striking finding was that HLA sharing was increased among the affected members, suggesting genetic similarities. Seven of 14 sib pairs (50%) who had concordant SLE were HLA identical as opposed to an expected 25%. Another interesting finding was that 15/18 (83%) patients with SLE and 11/22 (50%) consanguineous relatives had LCA, while 1/9 (11%) spouses, and 2/42 (5%) healthy controls had these antibodies. Conclusion: Genetic factors have a role in the development and expression of SLE. Environmental factors may trigger the disease in genetically susceptible hosts.

Summary Pemphigus foliaceus (PF) is an autoimmune bullous epidermal disease, characterized by autoantibodies specific to the desmosomal protein desmoglein 1 (dsg1) and by acantholysis, the rupture of the cellular junctions among keratinocytes. Known also as fogo selvagem (wild fire) in Brazil, the disease has distinct epidemiological characteristics, being endemic in certain regions of South America. It is a multifactorial (complex) disease, with oligo- or polygenic disease susceptibility. In view of the previously reported evidences of a role for apoptosis dysregulation in pemphigus pathogenesis, we hypothesized that genetic variants of molecules participating in apoptosis may contribute to interindividual variation of susceptibility to PF. The TP53 12139(G,C) and the BAX−248(G,A) single nucleotide polymorphisms (SNP) were analysed in a genetic association study. The allelic, genotypic and allele carrier frequencies for these SNPs did not differ statistically between the patient and the control groups, for both the Euro- and the Afro-Brazilian population strata. The results of this study lead us to conclude that, although the TP53 and BAX alleles analysed differ functionally, this variation does not alter the functionality of the molecules in a way that would interfere with the development of the disease.

Idiopathic CD4+ T lymphocytopenia (ICL) is an immunodeficiency syndrome characterized by severe depletion of CD4+ T lymphocytes, but in which human immunodeficiency virus cannot be detected. Peripheral blood mononuclear cells (BPMCs) from an ICL patient were cocultured with HUT78 T-lymphoblastoid cells, and an acute cytopathic effect and formation of multinucleated cells were observed. A human intracisternal A-type retroviral particle designated HIAP-II was detected in cells surviving the acute cytopathic effect. Eight of 13 ICL patients in a blinded screen of a serological panel provided by the National Centers for Disease Control and Prevention (CDC) had serum antibodies that specifically reacted with HIAP-II associated proteins by Western immunoblotting. None of 19 control sera in the panel that were unreactive with HIV Gag proteins produced a positive result on HIAP-II immunoblots. Comparable results were obtained in a blinded screen of a second CDC serological panel. Sera from 8 of 14 ICL patients in the second serological panel were positive for antinuclear autoantibodies (ANAs) commonly observed in patients with systemic autoimmune diseases. These results suggest the possible involvement of an A-type retrovirus or autoimmunity in development of ICL in a subset of patients.

Background. — A history (or lack thereof) of penicillin allergy is known to be unreliable in predicting reactions on subsequent administration of the drug. This study tests the usefulness of four penicillin allergen skin tests in the prediction of IgE-mediated reactions subsequent to administration of penicillin. Methods. — Eight centers cooperated in the National Institute of Allergy and Infectious Diseases trial of the predictive value of skin testing with major and minor penicillin derivatives. Hospitalized adults were tested with a major determinant (octa-benzylpenicilloyl-octalysine) and a minor determinant mixture and its components (potassium benzylpenicillin, benzylpenicilloate, and benzylpenicilloyl-N-propylamine). Patients then received a therapeutic course of penicillin and were observed, for 48 hours, for adverse reactions compatible with an IgE-mediated immediate or accelerated allergy. Results.— Among 726 history-positive patients, 566 with negative skin tests received penicillin and only seven (1.2%) had possibly IgE-mediated reactions. Among 600 history-negative patients, 568 with negative skin tests received penicillin and none had a reaction. Only nine of the 167 positive skin test reactors received a penicillin agent and then usually by cautious incremental dosing. Two (22%) of these nine patients had reactions compatible with IgE-mediated immediate or accelerated penicillin allergy; both were positive to the two determinants. Conclusions.— These data corroborate previous data about the negative predictive value of negative skin tests to these materials. The reaction rate in skin test—positive patients was significantly higher than in those with negative skin tests, demonstrating the positive predictive value of positive tests to both major and minor determinants. The number of patients positive only to the major determinant or only to the minor determinant mix was too small to draw conclusions about the positive predictive value of either reagent alone. ( Arch Intern Med. 1992;152:1025-1032)

The immunopathogenetic mechanisms associated with the development of inflammatory myopathies are not well defined. In order to identify cells in affected muscle tissue, mononuclear cells infiltrating muscle biopsies from patients with inflammatory myopathies and controls with other neuromuscular diseases were analyzed in situ by an avidin-biotin immunoperoxidase technique. Serial frozen sections were stained for cells expressing total T, helper-induced T, suppressor-cytotoxic T, B, monocyte/macrophage, and HLA-DR phenotypes. A significant increase in the percentage of helper-induced T cells was noted in the inflammatory myopathies when compared to the disease control group. Furthermore, most of the mononuclear cells in the inflammatory myopathy biopsies were HLA-DR positive, suggesting that the infiltrating T lymphocytes were activated. No significant differences in mononuclear cell distributions were found when the inflammatory myopathy group was broken down into individual groups of patients with polymyositis, polymyositis with associated connective tissue disease, and dermatomyositis.

Sera from patients with systemic lupus erythematosus (SLE) and clinically related diseases were examined for cold-reactive lymphocytotoxic antibodies (LCA). The incidence of LCA was significantly increased in SLE (93%), discoid lupus (50%), and "lupus-like" syndromes associated with congenital complement deficiencies (63%) as compared to normal controls (3%) and patients with drug-induced lupus (11%), mixed connective tissue disease (MCTD) (17%), and necrotizing vasculitis (19%). The diagnostic and pathogenetic implications of these differences are discussed.

Thirty-two biopsies of kidneys and of normal skin were performed simultaneously on patients with systemic lupus erythematosus (SLE) to determine whether the deposition of immune reactants in skin was correlated with the severity of renal injury or with several serologic measures of systemic disease activity. Immunofluorescent deposits at the dermal-epidermal junction (lupus band test) did not correlate with any clinical or histologic measures of glomerulonephritis or with serologic abnormalities. Immune deposits in dermal venules were found in 56% of the skin biopsies and were correlated with hypocomplementemia and higher levels of immune complexes in serum, and possibly with glomerular subendothelial electron dense deposits. Azathioprine therapy was correlated with absence of both sub-epidermal and vascular immune deposits. Immuno-fluorescent findings on serial skin biopsies on 13 patients were highly inconsistent. It is concluded that the lupus band test is clinically useful only as a diagnostic aid but not helpful in assessing renal or serologic activity of lupus, and that dermal vascular deposits of immunoglobulin or complement are more frequent than previoulsy recognized and correlate with measures of circulating immune complexes.

The efficacy of adoptively transferred humoral and cell-mediated immunity in chronic hepatitis B infection was studied in three patients. The first patient with renal failure and chronic active hepatitis received high titered human antibody to the hepatitis B antigen. The second, an asymptomatic chronic antigen carrier, received “immune” lymphocytes and transfer factor (which was not tested for biologic activity in a normal recipient) prepared from the same collection of cells. In the third patient who had acquired hepatitis B from her mother at birth, transfer factor prepared from maternal leukocytes was given on two occasions. Clinically, there was no change in the first patient's liver function despite transient descreases in hepatitis B antigen and increases in antibody titers. Coexistent antigen and antibody persisted for over 4 mo. In the second patient, the immune lymphocytes induced biochemical signs of transient acute hepatitis associated with increased antigen levels, whereas transfer factor did not have an effect. In the third patient, maternal transfer factor caused increased hepatitis B antigen and transaminase levels on two occasions. Subsequently, liver function became normal and the antigen titer was reduced by 95%. Adoptive transfer of humoral immunity does not appear to modify established hepatitis B infection, whereas cell-mediated immunity does. It is postulated that liver cell injury in hepatitis B may be more related to the host's cell-mediated immune response rather than to a cytopathogenic effect of the putative hepatitis B virus.

To study the mechanisms responsible for leukocytoclastic vasculitis, we evaluated the kinetics of immunologic and cellular changes in induced vasculitis lesions. In four of five consecutive patients with active vasculitis, lesions were induced by increasing vascular permeability via injecting histamine into the skin. Biopsies were obtained for light and electron microscopy and immunofluorescence at 1, 4, 8, and 24 hr after injection. The results show that immunoglobulin, C3, and electron-dense material are deposited in vessel walls early and are followed by cellular infiltration. The characteristics of the cellular infiltrates were quite diverse at different times after histamine provocation and no distinctive patterns were seen. Nevertheless, the kinetics of the appearance of immunoreactants and cells implies that immunoglobulin and probably circulating immune complexes are present prior to the development of inflammation and supports the contention that deposition of immune complexes within vessel walls is responsible for leukocytoclastic vasculitis.

Human thymus derived lymphocytes (T cells) interact with sheep red blood cells (SRBC) to form rosettes. We wanted to determine whether the lymphocyte's receptor for SRBC is associated with serologically detectable cell surface antigens. Antisera were prepared by immunizing horses with either fresh human thymus (ATG) or with B lymphocytes from an established lymphoid cell line in culture (ALG). ATG, ALG or Concanavalin A (Con A) were added to lymphocyte preparations to determine their effect on rosetting. The results showed that ATG inhibited rosettes in a dose dependent manner. In contrast, both the Con A and ALG had no effect. By immunofluorescence, Con A and ALG staining cells were able to form rosettes. ATG staining cells were unable to form rosettes. Removal of the ATG receptor by capping could not restore the rosette forming capacity suggesting that inhibition was not due to steric hindrance. We conclude that antibody directed against T cells but not B cells binds to surface antigens which appear to be identical with or in close proximity to the specific SRBC receptor.

In order to characterize the nature of the mononuclear cells in the perivascular infiltrates in the skin of 11 patients with CU, skin biopsy specimens were analyzed in situ by an avidin-biotin immunoperoxidase technique. Serial frozen sections were stained for total T cells, helper-inducer T cells, suppressor-cytotoxic T cells, B cells, monocytes/macrophages, and HLA-DR antigen. The infiltrates were found to consist mainly of T cells, whereas B cells and macrophages were rarely seen. Most of the T cells possessed the T4+ helper phenotypes, whereas smaller numbers of infiltrating cells were defined as suppressor-cytotoxic cells. Most of the helper-inducer T cells coexpressed the Ia (HLA-DR) antigen. Several potential pathogenic mechanisms could be implicated in CU based on these observations.

In a comprehensive study of 80 patients with vasculitis, 4 had concurrent hepatitis B virus (HBV) infection. Polyarteritis nodosa was present in 2 and in the other 2, cutaneous vasculitis, presenting clinically as palpable or Henoch-Schonlein purpura. In one of these patients skin biopsies demonstrated granular deposits of IgM, C3, C4, and the hepatitis B surface antigen (HBsAg) and electron-dense deposits of aggregated 20-nm particles resembling HBsAg in postcapillary venules. Evidence for circulating HBsAg-immune complexes included increased serum Clq binding activity, decreased serum complement, and a cryoprecipitate containing both HBsAg and IgM anti-HBs. Aggregated 20-nm particles resembling intact HBsAg were also seen by negative staining electron microscopy of the serum cryoprecipitate. This patient fulfills all the criteria for a specific immune complex vasculitis caused by his immune response to a chronic HBV infection. These findings emphasize that HBV infection may be associated with small vessel vasculitis as well as polyarteritis nodosa, mixed cryoglobulinemia, and glomerulonephritis. A similar immune response to other viral infections may be expressed as palpable (Henoch-Schonlein) purpura also.

Complement system proteins, C4 metabolism and serologic markers of systemic lupus erythematosus were studied in identical male twins with chronic discoid lupus erythematosus and hereditary angioedema. Systemic lupus erythematosus was confirmed in their mother at age 22 during the twins' gestation. She also manifested symptoms suggesting hereditary angioedema. Low C1 inhibitor (C1 INH) and C4 have been documented since age 13 in both twins. At this time, metabolic studies disclosed a combined C4 fractional hypercatabolism (0.96 to 1.02/day) and decreased synthesis (3.0 to 3.15 mg /kg/day). Normal C1 inhibitor and C4 concentrations are present in their healthy father and maternal grandparents, indicating that the C1 inhibitor deficiency in the twins was inherited as an autosomal codominant from their mother in whom a spontaneous mutation had occurred. Positive antinuclear antibody, increased antibody to denatured deoxyribonucleic acid and immunoglobulin deposits in normal skin in both twins are evidence of systemic lupus erythematosus. In addition, a chronic biologic false-positive serology is present in one twin. We postulate that the association of hereditary angioedema and "familial" systemic lupus erythematosus is a biologically relevant phenomenon. It is proposed that the secondary C4 deficiency predisposed the patient to the development of systemic lupus erythematosus in some presently unknown manner.

Intestinal lymphoid hyperplasia and recurrent pulmonary infections by pyogenic bacteria are well-recognized accompaniments of common variable (late onset) hypogammaglobulinemia. A 35-yr-old woman with this illness had progressive pulmonary insufficiency caused by nodular lymphoid interstitial pneumonitis, rather than by infectious lung damage, and intestinal lymphoid nodular hyperplasia. B cells were abundant in the intestinal nodules but absent in the pulmonary nodules by immunoperoxidase staining. Pulmonary lymphocytes isolated in single-cell suspension from the biopsy were 0.5% B cells and 82% T cells. Prednisone therapy improved pulmonary function and decreased the intestinal lymphoid nodules. Lymphocytic interstitial pneumonitis should be considered in patients with hypogammaglobulinemia and restrictive lung disease.

To ascertain the possible influence of acetylator phenotype on antinuclear antibodies in systemic lupus erythematosus (SLE), we assayed sera from 11 rapid acetylators and 10 slow acetylators for IgM and IgG antibodies to chromatin, histones, denatured DNA, and native DNA. Whereas the majority of SLE patients of both acetylator phenotypes had elevated levels of antibodies to all 4 antigens compared with normal controls, there was no difference in antibody activities between slow acetylator patients versus rapid acetylator patients for these antigens. We conclude that levels of antibody to chromatin, histones, and DNA in SLE patients are similar irrespective of acetylator phenotype, and that if a protective effect of slow acetylation on spontaneous development of antinuclear antibodies does occur, a prospective study of presymptomatic individuals at high risk for lupus may be required to reveal this effect.

The complement system was evaluated in 22 individuals with disseminated gonococcal infection. Three of the 22 patients exhibited a total serum complement activity that was greater than 2 SD below the normal mean. Of these three, one had a complete deficiency of C1r, a second patient had pre-existing systemic lupus erythematosus with low levels of C4, and the third had a C8 concentration that was 60% of normal. We conclude that the prevalence of inherited or acquired complement deficiency among patients with disseminated gonococcal infection exceeds that among the general population and is an important host factor predisposing to systemic infection with Neisseria gonorrhoeae.

Late cutaneous reactions preceded by an immediate wheal-and-flare reaction have been described after allergen skin testing, intradermal 48/80 injection, and skin testing with heterologous antihuman IgE. We report the finding of delayed cutaneous reactions after prick food skin testing in a subgroup of five patients with delayed pressure urticaria. This subgroup is also defined by symptomatic clearing after fasting. We demonstrate a correlation of food challenge with skin test response in this same subgroup. Some patients who had previously required prednisone for control of urticaria were able to be managed without it while they were receiving the exclusion diet. In addition, their pressure symptoms and challenge disappeared while they were receiving the restricted diet. These findings suggest that an underlying food sensitivity may be an important precipitating factor in some patients with delayed pressure urticaria.

The clinical course and diagnostic profile of 13 patients with central nervous system involvement and systemic lupus erythematosus (CNS-SLE) are presented. The diagnostic yield for each procedure was measured as the percent abnormal: CSF total protein was 38%; increased CSF IgG 69%; decreased CSF hemolytic C4 10%; increased CSF anti-DNA 64%; electroencephalogram 80%; flow brain scan 50%; and static brain scan 0%. No single procedure was consistently abnormal, but the battery of tests provided a useful and specific CNS-SLE diagnostic profile.

Combined H1 (cyproheptadine) and H2 antihistamines (cimetidine) were tried in eight patients with chronic urticaria who were previously unresponsive to conventional anti-urticarial regimens, including type I antihistamines, hydroxyzine, ephedrine and corticosteroids. 50% of the patients responded with 90% or greater improvement within 10 days. The remaining 50% showed no benefit. Side effects of the medications were minimal. These results indicate that a 10 day trial of both H1 and H2 antihistamines may be useful in patients with chronic urticaria resistant to all other standard treatment modalities.

Circulating immune complexes were characterized from 25 sera obtained from five patients with polyarteritis nodosa and three with cutaneous venulitis associated with hepatitis B virus infection. Complexes were isolated by polyethylene glycol and conglutinin-anticonglutinin precipitation methods and were analyzed for HBsAg and anti-HBsAg. Low pH was used to dissociate the complexes, and components were separated into antigen and antibody fractions by using immobilized protein A. In this study, three observations were significant: 1) complexes were frequent and quantitatively more in cutaneous venulitis than in polyarteritis; 2) the levels of HBsAg in the antigen fractions of polyarteritis were greater and correlated with the clinical improvement of the disease; the serum levels of HbsAg remained the same throughout the course of the disease; and 3) complexes from polyarteritis were not completely dissociable at pH 2.6 compared with those from patients with cutaneous venulitis and chronic active hepatitis. The antigen fractions electrophoresed in polyacrylamide gel with SDS demonstrated 6 to 10 protein bands with m.w. ranging between 17,000 and 120,000 daltons. To precisely define the polypeptide antigen moiety involved in the immune complex formation, a transfer blotting technique was used employing human anti-HBsAg globulin as probe. Polypeptides with m.w. 97,000, 49,000, and 23,000 were found to form complexes in both groups of patients.

We report a patient with hypocomplementemic urticarial-vasculitis syndrome. This case illustrates the continuum between urticaria and purpura characteristic of hypocomplementemic urticarial-vasculitis syndrome. Clq precipitin was demonstrated in the patient's serum and in the diethylaminoethylcellulose-ion exchange fraction containing only IgG. A skin biopsy specimen of urticarial and purpuric lesions demonstrated leukocytoclastic vasculitis and granular deposition of C3 and Clq in the basement membrane with IgA, IgM, C3, and Clq in postcapillary venules. Serial total hemolytic complement activity and Clq determinations were performed, and the response to several treatment regimens is presented. Symptomatic and serologic improvement was observed only with hydroxychloroquine.

We describe a simple, reproducible, and low-cost test for xerostomia, which involves chewing on a folded sterile sponge for 2 minutes. Saliva production is quantitated by weighing the sponge before and after chewing. Normal control subjects produced greater than or equal to 2.75 gm of saliva in 2 minutes. Three of 32 consecutive, unselected outpatients in allergy-immunology clinics and 9 of 38 patients in rheumatology clinics had decreased saliva production, which was significantly different compared with controls (P less than 0.01). The presence of sicca symptoms was highly correlated with quantitatively abnormal tear and saliva production, according to the results of the Saxon and Schirmer's tests.

RENAL homograft recipients have been reported to have a high incidence of livu disease in the post-transplantation period.2f• 29. 31. 56. 65, 70 It was assumed that the immunosuppressive agents were responsible, either by their hepatotoxicity or because the consequent weakening of the host immune system permitted the frequent development of virus hepatitis. An accurate distinction between these two general possibilities was not feasible until recently. Then, with the description of tests which permitted identification of the hepatitis associated or Australia (Au) antigen, 7 , 9, 58 it became possible to deciSively study at least one variety of virus hepatitis in transplant recipients. In this communication, a series of observations related to the problem of hepatic damage with or without hepatitis in a large transplantation program will be presented. These observations will include: (1) The

Summary The present paper reports studies of a third kindred which manifests the hereditary C2 deficiency trait. The homozygous individual had no detectable hemolytic serum complement or C2 activity, although C2 could be detected by immune adherence; three heterozygous members of the family had 60 to 70% of the normal serum C2 titers. Normal or elevated serum C1, C3, C4 and C5 levels were obtained in all members of the kindred. There was no evidence for a C2 inhibitor in the propositus' serum; in addition, the deficiency could be corrected by the addition of purified C2. An analytical technique which permits quantitation of very small amounts of C2 was developed and applied to the measurement of C2 in the serum of members of the family. It is based upon the quantitation of C3 uptake by EAC1, 4 as a function of C2 concentration, i.e., the immediate reaction product of a C2-dependent reaction is measured. The serum C2 level was found to be 0.5 to 4% of normal in the homozygous individual and 60 to 70% of normal in the heterozygotes. When normal sera were assayed by this technique, the C2 titers obtained were in good agreement with the values obtained by hemolytic titrations.

Summary Immunochemical quantitation of the third, fourth and fifth components of human complement is feasible with the single radial immuno-diffusion technique. Serum component concentrations (mg/ml) in 25 healthy adults were: C′3, 1.23 ± 0.26 (0.86 to 1.84); C′4, 0.436 ± 0.118 (0.240 to 0.800) and C′5, 0.076 ± 0.024 (0.042 to 0.140). The experimental error of the quantitation was 10% for C′3 and C′4 and 15% for C′5. The immunochemical quantitation is influenced by in vitro conditions which allow physicochemical alterations in complement proteins; inclusion of ethylenediaminetetraacetate in the agar and the use of fresh serum or serum stored at -70°C circumvents this problem.

Electroimmunodiffusion (EID) was adapted for the detection of hepatitis-associated antigen (HAA) and compared with immunoelectroosmophoresis (IEOP) and double diffusion (DD) with respect to sensitivity and applicability to rapid screening of large numbers of sera. EID is as sensitive as IEOP, requires less antiserum, and is quantitative. Results may be obtained within 45 minutes if high-titer antiserum is available. Using this technique, 26 HAA-positive sera were identified among 10,303 potential blood donors during a 3 month period.

Immunoglobulins and C3 were detected by immunofluorescence in the blood vessel walls of biopsies of clinically normal skin in patients with active necrotizing vasculitis. Of the 13 patients studied, 9 had C3 and 6 of these had IgM or IgA in biopsies of lesions of vasculitis. In adjacent clinically normal skin, 7 patients had C3 and 3 of these also had IgM or IgA. These findings support the hypothesis that immunoglobulins and complement are present in vessels of some patients prior to chemotaxis of polymorphonuclear leukocytes and the resulting inflammatory purpuric lesions so characteristic of necrotizing vasculitis.

Do allergists really need to be well informed about circulating antigen-antibody or immune complexes (CIC)? The answer to this rhetorical question is “yes” for a number of reasons. First, over the past year four articles have appeared. Three of them were in this JOURNAL. The most recent is by Yang and colleagues on page 300 of this issue. It concerns CIC in patients with atopic respiratory disease, comparing those on hyposensitization thera.py with untreated atopic controls and with normals without IgE-related disease. rw4 In these studies, two of them from the same laboratory,‘, 4 the hypothesis was tested that long-term hyposensitization, intended to increase IgG blocking antibody, might also induce CIC composed of allergen and IgG blocking antibody. To me this is a very unlikely hypothesis when the small amounts of allergenic extracts injected and the sensitivity of the CIC detection assays are considered. For examlple, Stein and associates3 collected serum from patients 2 hr after injections of 0.5 ml of 1: 100 w/v allergenic extracts when “significant antigen absorption” appeared. CIC were measured with a radiolabeled Clq-polyethylene glycol assay, which had a detection sensitivity equivalent to 5 pg/ml of human

The efficacy of specific-antibody treatment in preventing hepatitis B virus infection in infants born to mothers positive for the hepatitis B surface antigen was evaluated. Four babies were treated one to six days after delivery with antibody to the antigen and remained antigen negative for five to 14 months. In six of seven similar but untreated babies, chronic antigenemia developed within five to 12 weeks of birth and persisted in all up to the age of 36 months. Two of seven umbilical-cord serums were positive, by radioimmunoassay only, but this finding does not establish in utero infection. The current prevalence of the surface antigen in mothers at term is 0.83 per cent at three Denver hospitals. Treatment with specific antibody appears to be effective, as compared to no treatment, in preventing neonatal hepatitis B virus infection. (N Engl J Med 291: 1378–1380, 1974)

HEPATITIS B antigen (HBAg) occurs in three general clinical groups: in acute B-type viral hepatitis in which HBAg is present in the early phase of illness and disappears in 95 per cent of patients concomitant with clinical recovery; in association with certain diseases such as Down's syndrome, uremia treated with hemodialysis, renal-transplant recipients, leukemia and lepromatous leprosy, in which persistence of HBAg is common; and in asymptomatic carriers who report neither exposure to blood products nor contact with patients with hepatitis.1 2 3 Persistence of HBAg in the first two groups has been postulated to be due to individual host variation in . . .

To study the relationship of cold-reactive lymphocytotoxic antibodies (LCA) to immune defects in cancer, LCA were measured in sera from 71 patients with different types of malignancies and 31 healthy controls. A significantly increased incidence (10 of 24) of LCA was noted in a group of patients with lymphoreticular malignancies excluding chronic lymphocytic leukemia (CLL). No significantly increased incidence of LCA was found in patients with CLL (0 of 9), melanoma (5 of 22), or carcinoma (1 of 16) as opposed to normal controls (1 of 31). In the lymphoreticular malignancy group, no correlation was noted between LCA levels and delayed hypersensitivity skin tests, skin croton oil response, total lymphocytes, T cells, or B cells. We conclude that LCA is increased in patients with certain lymphoreticular malignancies in contrast to other types of cancer. Its presence, however, is unrelated to major defects in the cell-mediated immune system seen in some of these patients.

We have explored the problem of the histologic basis of chronic urticaria and its relation to vasculitis and immune complex disease. In a prospective study, 42 consecutive patients with chronic urticaria (from twice weekly to daily episodes lasting more than 6 wk) had skin biopsies and were studied for immunologic variables. Twenty-two patients (52%) had vasculitis on biopsy as defined by the presence of cellular infiltrates within the vessel wall. The other 20 patients (48%) had either edema only or perivascular infiltrates with mononuclear cells (perivasculitis). The group with vasculitis could be subdivided into seven patients with neutrophilic venulitis including three with fibrinoid change, seven with mixed-cellular vasculitis, four with lymphol monocytic vasculitis, and four with eosinophilic vasculitis. Vascular deposits of immunoreactants were found in only four (18%) of the vasculitis patients, compared with 65% of concurrently studied patients who had cutaneous venulitis manifested as palpable purpura, i.e., Henoch-Schonlein syndrome. Urticarial patients with vasculitis were more often male and had a longer mean duration of hives compared with the nonvasculitis group. We saw no differences between the vasculitis and nonvasculitis cases of urticaria with regard to the incidence of arthralgia, elevated erythrocyte sedimentation rate (ESR), or hypocomplementemia. The group with vasculitis did not have more generalized disease nor were the hives more resistant to therapy. We have discussed the definition and histologic criteria for the diagnosis of vasculitis when it occurs in very small blood vessels.

Late cutaneous reactions ( LCRs ) have been described in patients after allergen skin testing, skin testing with heterologous anti-human IgE, autologous skin-blister fluid, and, variably, after 48/80 injection. We report our results of skin testing patients with delayed pressure urticaria ( DPU ), chronic urticaria, and normal volunteers with histamine and 48/80. All patients with DPU had LCRs after 48/80. No patients in either of the other groups developed LCRs . This may be a clue to pathogenic mechanisms involved in DPU .

We studied four patients with recurrent attacks of angioedema, urticaria, and fever. During attacks, body weights increased up to 18 per cent, and leukocyte counts reached 108,000 per microliter (88 per cent eosinophils). The disease did not appear to threaten the function of vital organs. The two children received prednisone intermittently; the adults did not require treatment or were given alternate-day prednisone. Glucocorticoid therapy caused defervescence and diuresis and decreased total leukocyte and eosinophil counts. No patient had evidence of cardiac involvement (follow-up, 2 to 17 years). One patient remained in spontaneous remission for 20 years before symptoms recurred. Histologic studies showed that eosinophils localized and degranulated in the dermis, and they appeared to induce edema. Although this syndrome might be classified as a variant of the hypereosinophilic syndrome, we believe it is a separate entity because of its distinctive characteristics and its benign course.

Antilymphocyte antibodies have been demonstrated in autoimmune diseases, acute viral infections, and acquired immune deficiency syndrome (AIDS) by using either the conventional microlymphocytotoxicity or the double fluorescence technique. In the present study, we used both methods to detect the antilymphocyte antibodies and to characterize further their immunologic significance in patients with AIDS and their sexual partners. The results using the conventional microlymphocytotoxicity method demonstrated that 8 of 10 patients with AIDS and 6 of 10 partners had significant levels of antilymphocyte antibodies which were reactive with B and T cells at cold and warm temperatures. A significant loss in antibody activity following absorption with B, T, and Daudi cells and Staphylococcus aureus, but not platelets or red cells, indicated that these antibodies are not directed to HLA class I antigens but, rather, to antigens that are common to both groups of lymphocytes. There is a close association between antilymphocyte antibodies and lymphopenia in patients but not in partners. Antibodies against lymphocyte subclasses [helper (T4) and suppressor (T8)] were detected by the double fluorescence staining technique, which employs C6-deficient serum as a nonlytic source of complement, and demonstrated the binding of antibodies to target cells, in contrast to lysing of the target cells as in the microlymphocytotoxicity method. The results of this assay showed that antibodies were directed to both populations, and there was no correlation or association between the absolute numbers of peripheral T4 and T8 cells and the percentage of antibody binding. Taken together, there appear to be at least two kinds of antilymphocyte antibodies: lymphocytotoxic antibodies detected by the conventional microlymphocytotoxicity assay and noncytotoxic antibodies detected by the double fluorescence staining technique. The former may be responsible in part for the lymphopenia. The latter may alter lymphocyte function. The patients and partners who had antilymphocyte antibodies also had anti-HTLV-III antibodies, although there was not any close correlation between titers. These findings support the possibility that both types of antibodies occur as part of a generalized immune response, possibly stimulated by the same viral agent.

The presence of cold-reactive lymphocytotoxic antibodies has been demonstrated in patients with viral infections and various “autoimmune” diseases thought to be related to viral infection. In the present study we have examined the incidence and possible significance of these antibodies in patients with multiple sclerosis, another disease probably associated with a viral agent. The incidence of lymphocytotoxic antibodies was significantly increased in patients with multiple sclerosis as compared to their siblings, patients with other neurological disease, and normal controls. The level of these antibodies correlated significantly with serum measles antibody titers in the affected patients. No correlation was found between lymphocytotoxic antibody levels and parameters or clinical disease or other viral antibody titers in the serum and cerebrospinal fluid. It was concluded that lymphocytotoxic antibodies in patients with multiple sclerosis probably serve as markers of viral infection.

Gel electrophoresis, lectin affinity blotting, and endoglycosidase H digestion have been used to analyze the glycoprotein profiles of bloodstream and procyclic forms of Trypanosoma brucei brucei and T. b. gambiense. Proteins resolved by polyacrylamide gel electrophoresis were stained with silver nitrate or electrophoretically transferred to nitrocellulose and probed with a horseradish peroxidase conjugate of either concanavalin A or wheat germ agglutinin. Silver staining showed, as expected, that the expression of the variant specific glycoprotein was restricted to the bloodstream forms. Twenty-three concanavalin A binding proteins were resolved in blots of bloodstream forms. Concanavalin A binding molecules corresponding in electrophoretic mobility to 21 of these 23 bloodstream form glycoproteins were detected in blots of procyclic forms. The two concanavalin A binding glycoproteins present only in bloodstream form extracts were variant specific glycoprotein and an 81-kDa protein designated glycoprotein 81b. One concanavalin A binding molecule of 84 kDa, glycoprotein 84p, was detected only in procyclic forms. The 19 major wheat germ agglutinin binding glycoproteins expressed by bloodstream forms were not detected in procyclic forms; only small proteins or protein fragments in procyclic form extracts bound wheat germ agglutinin. Incubating transferred proteins in endoglycosidase H eliminated subsequent binding of concanavalin A to most of the 22 common glycoproteins of bloodstream forms. Three major concanavalin A binding glycoproteins of bloodstream forms, variant specific glycoprotein, glycoprotein 81b, and a 110-kDa molecule (glycoprotein 110b), and other minor glycoproteins carried sugar chains that resisted endoglycosidase H digestion. In contrast, concanavalin A did not bind to any procyclic form glycoproteins, including a 110-kDa concanavalin A binding molecule (glycoprotein 110p) after endoglycosidase H treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated the complement system in 20 patients presenting with a first episode of meningococcal meningitis, meningococcemia, or meningococcal pericarditis. Assays of total serum complement activity were performed prospectively in 12 patients and retrospectively in 8. Six of the twenty patients had a complement deficiency (CH50 greater than 2 S.D. below the normal mean). Three of these six had a deficiency of a terminal-pathway protein (C6 in two and C8 in one), and the other three had deficiencies of multiple complement proteins associated with underlying systemic lupus erythematosus or multiple myeloma. Patients with decreased amounts of complement were similar to normal patients in terms of sex, age, type of infection, and meningococcal serogroup, but 3 of the 6 patients with a complement deficiency were black, as compared with none of the 14 patients with normal function (P = 0.018). Complement deficiency is common in patients with a first episode of meningococcal disease and may be due to either a deficiency in a single terminal protein or a complement-depleting underlying illness.

To further study the role of histamine in the pathogenesis of chronic urticaria, the concentration of histamine in tissue extracts from skin biopsy samples and in plasma from patients with chronic urticaria was measured by a sensitive radioenzymatic assay. Tissue histamine levels from urticarial lesions and uninvolved skin were compared with extracts of biopsy samples taken from normal controls. The average tissue histamine content in 15 biopsy samples from the chronic urticaria patients was significantly higher than in those of 15 normal controls. Forty percent of the patients had levels 2 SD greater than the mean of the control group. Elevated histamine levels were also found in biopsy samples of uninvolved skin from some urticaria patients. Circulating histamine levels from chronic urticaria patients were rarely elevated and did not correlate with skin concentration. No correlation was noted between tissue histamine concentration and estimated mast cell concentration on Giemsa-stained sections of five biopsy samples. These results indicate that tissue histamine levels are increased in some patients with chronic urticaria. This suggests that local histamine elevations may be important in the pathogenesis of many patients with this disease. In addition, increased tissue histamine in these patients is not reflected by elevated circulating levels.

To ascertain if a genetically determined slow drug acetylation rate is correlated with the development of spontaneous systemic lupus erythematosus (SLE), as it is in drug-induced SLE, acetylation phenotypes of 27 patients with spontaneous SLE were determined after administration of dapsone. Thirty-three percent were slow acetylators, 63% were rapid acetylators, and one was indeterminate, a distribution not significantly different from that expected in control subjects. Among 4 pairs of first-degree relatives, all of whom had spontaneous SLE, 7 of the 8 individuals were rapid acetylators. We conclude that people who are slow acetylators are at no greater risk for developing spontaneous SLE than are rapid acetylators and that the slow acetylation phenotype is not correlated with familial SLE.

SummaryIt has been postulated that the initial hemodynamic alterations in canine endotoxin shock are due to an immune mechanism (antigen-antibody) involving complement. Partial decomplementation of dogs follwoing intravenous injection of heataggravated human globulin, enhanced rather than decreased the lethal effect of endotoxin. The results of the present experiments suggested that because of the macromolecular size of the heated globulin anaphylaxis was produced, and in this manner the anaphylactic action of endotoxin was enhanced.

Excerpt The relative contributions of humoral and cellmediated immune mechanisms in the rejection of renal homotransplants is an important but still unresolved issue. The diversity of the clinical ...