Antibodies to granulocytes in patients infected with human immunodeficiency virus.

Individuals who are infected with human immunodeficiency virus (HIV) are known to have a high incidence of autoantibodies. In this study, serum samples from 100 individuals with HIV infection were tested for granulocyte antibodies (red cell antibodies, lymphocytotoxic antibodies, circulating immune complexes, and serum immunoglobulin G levels) by granulocyte agglutination (GA) and granulocyte immunofluorescence (GIF) assays. Granulocyte antibodies were detected in 66% of serum samples by GIF and in 21% of serum samples by GA. None of the positive sera reacted with granulocyte antigens of known specificity. Antibodies that reacted with red cell antigens other than ABO were detected in only three serum samples, but lymphocytotoxic antibodies were detected in 62% of patients. All serum samples were tested by immunoblotting with granulocyte plasma membranes. Only two samples were found to be positive; one sample reacted with a 58 kd protein and one reacted with a 55 kd protein, but neither serum sample immunoprecipitated any protein from granulocytes that were labeled at the cell surface with iodine 125. Since immune complexes that are bound to granulocyte membranes can be detected by GIF, circulating immune complex levels were measured in all 100 samples. Immune complexes were increased in GIF-reactive serum samples compared with GIF-nonreactive serum samples (23.3 +/- 19.5 micrograms Eq/ml [mean +/- SD] vs 9.6 +/- 8.1 micrograms Eq/ml, p less than 0.001) but not in GA-reactive serum samples compared with GA-nonreactive sera (24.4 +/- 21.3 micrograms Eq/ml versus 16.9 +/- 16.0 micrograms Eq/ml, p = 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)

Lymphocyte subsets associated with T cell receptor beta-chain gene rearrangement in patients with rheumatoid arthritis and neutropenia.

OBJECTIVE: To determine the incidence of a clonal lymphoid disease in patients with chronic rheumatoid arthritis (RA) and neutropenia. METHODS: Lymphocytes from 23 RA patients with either current neutropenia or a history of this complication were studied. RESULTS: Eight patients had a clonal rearrangement of the T cell receptor beta-chain gene. Phenotypically, they showed a distinctive pattern characterized by an inverted CD4+:CD8+ cell ratio and an increased number and percentage of CD57+/CD8+ and CD3+/DR+ lymphocytes. None had evidence of a lymphoid malignancy. CONCLUSION: Among RA patients with neutropenia, there is a subset who have a subclinical disease resembling T gamma lymphoproliferative disease.

HLA class I and II antigen phenotypes of North American Indians from Minnesota: implications for marrow transplants using unrelated donors.

As a result of an appeal for a bone marrow donor for a North American Indian (Native American) patient, 261 Native Americans from our community were typed for HLA-A,B,DR antigens, and 51 were typed for HLA-A,B antigens only. The HLA antigen frequencies of the Native Americans were compared with those of 12,881 white bone marrow donors and were found to differ markedly. To investigate the implications these differences in HLA antigen frequencies would have for the location of unrelated bone marrow donors, the HLA types of 12 Native American bone marrow transplant patients from our institution were used to search among 5389 HLA-A,B,DR-typed white donors in the National Marrow Donor Program file and the file of 261 HLA-A,B,DR-typed Native American donors. In the white donor file, at least two donors were found that matched at all HLA-A,B,DR antigen loci of one Native American patient (8%). Using the Native American donor file, which was less than one-twentieth the size of the white donor file, and HLA-A,B,DR-matched donor was also found for one (8%) of the patients. These results suggest that although donors for nonwhites can be identified in a file of HLA-typed white volunteers, the probability of finding a suitably matched donor for such individuals is enhanced if donors representing racial or ethnic minorities are included in unrelated donor registries.

Absence of HIV infection in blood donors with indeterminate western blot tests for antibody to HIV-1.

To determine whether apparently healthy persons who have had repeatedly reactive enzyme immunoassays and an indeterminate Western blot assay for antibody to the human immunodeficiency virus type 1 (HIV-1) are infected with HIV-1 or HIV-2, we studied 99 such volunteer blood donors in a low-risk area of the country. The subjects were interviewed about HIV risk factors. Coded blood specimens were tested again for HIV-1 antibody (by two different enzyme immunoassays, a Western blot assay and a radioimmunoprecipitation assay) and for HIV-2 antibody by enzyme immunoassay, for HIV-1 by the serum antigen test, for HIV-1 by culture, for human T-cell leukemia virus Type I or II antibody by enzyme immunoassay, and for sequences of HIV DNA by the polymerase chain reaction. Of the 99 blood donors, 98 reported no risk factors for HIV-1 infection; 1 donor had used intravenous drugs. After a median of 14 months (range, 1 to 30) from the time of the initial test, 65 subjects (66 percent) were still repeatedly reactive for HIV-1 antibody on at least one immunoassay. In 91 subjects (92 percent) the Western blot results were still indeterminate, whereas in 8 they were negative. No donor met the criteria for a positive Western blot assay for HIV-1, and none had evidence of HIV-1 or HIV-2 infection on culture or by any other test. We conclude that persons at low risk for HIV infection who have persistent indeterminate HIV-1 Western blots are rarely if ever infected with HIV-1 or HIV-2.

The first example of autoanti-Kx.

An IgG autoantibody with Kx specificity was found in the blood of a 61-year-old white man. The antibody did not cause hemolysis of his own or transfused Kx-positive red cells. The patient is of common Kell blood type and does not exhibit any clinical or hematologic features of McLeod syndrome.

Natural history of primary autoimmune neutropenia in infancy.

Five patients with primary autoimmune neutropenia were evaluated during their first 2 years of life. Their illness resolved spontaneously after 6 to 41 months (median 13 months), and the patients were subsequently followed for 13 to 73 months (median 28 months). None required immunosuppressive therapy to induce remission, and routine antibiotic therapy adequately controlled all infectious episodes. An increased rate of infection, particularly otitis media and upper respiratory tract infection, occurred during the neutropenic period. No other noninfectious illnesses, particularly no other autoimmune diseases, were reported in any of these patients at any time. In each case, resolution of neutropenia paralleled the disappearance of neutrophil autoantibodies which were specific for the NA1 antigen. This report describes the clinical and laboratory findings and the long-term history of primary autoimmune neutropenia in these five patients.

Hepatitis B core antibody (anti-HBc) in blood donors in the United States: implications for surrogate testing programs.

In order to evaluate the operational implications of excluding donated blood with antibody to hepatitis B core antigen (anti-HBc), the American Red Cross tested 107,473 voluntary blood donations for anti-HBc in 72 test sites during a 1-week period. The system-wide prevalence of anti-HBc was 2.60 percent, with a range of 0.55 to 6.38 percent, depending on geographic region. For the American Red Cross, which collects approximately one-half of the blood supply in the United States, excluding donated blood with anti-HBc would result in a loss of approximately 159,500 units during the first year.

Three sera defining a new granulocyte-monocyte-T-lymphocyte antigen.

Three sera containing antibodies recognizing a previously undescribed antigen on granulocytes were found during testing of sera from multiparous donors. All of the antibody producers were in good health. None had a history of transfusion. Using the granulocyte agglutination assay the sera recognize a single antigen which is not associated with the neutrophil antigens NA1, NA2, NB1, NC1, ND1, NE1, 5a, 5b, 9a, nor common red blood cell or HLA antigens. The three sera did not react with autologous cells or with the cells of the other antibody producers. Granulocytes from one antibody producer did not absorb antibody activity from any of the three sera. The antigen was found in large quantities on granulocytes and monocytes, in smaller quantities on T lymphocytes, and not on B lymphocytes, red cells, and platelets. The sera reacted with 340 of 343 random donors (99.1%) and were negative with the same donor cells. Family studies showed autosomal dominant inheritance of the antigen. Five of 12 sibs in three families lacked this antigen (not statistically different from the expected ratio). The calculated gene frequency for the gene controlling the production of this antigen is 0.906. There appeared to be no association to the HLA, NA or Rh loci or to the X or Y chromosomes. None of the infants of these three women showed clinical signs of alloimmune neonatal neutropenia.

A microtiter modification of granulocyte immunofluorescence.

The granulocyte immunofluorescence test (GIFT) is valuable for detecting allogeneic and autologous granulocyte antibodies. However, the original tube technique (macro GIFT) requires 50-100 microliters of serum and 10(6) granulocytes with time-consuming washing steps which cause cell loss. We report a modification (micro GIFT) using microtiter trays which requires only 20 microliters of serum and 2 X 10(5) granulocytes. The modified method conserves reagents, reduces the time required for washing by 67%, decreases cell loss in washing by 74%, reduces the volume of conjugate required by 67%, and compares favorably with the macro GIFT in accuracy, specificity, and sensitivity.

A rare example of weakened expression of the Kell (K1) antigen.

Random typing of donor units revealed a donor whose red blood cells gave very weak reactions with all anti-Kell (anti-K1) antisera. All other Kell-system antigen was present in four generations of the donor's family. The red-cell morphology is normal in all family members with the weakened K1 antigen. A consistent hypothesis is that the weak antigen is inherited through a variant allele at the Kell locus and represents a quantitative, not a qualitative, change.

Acquired B antigen and polyagglutination in a apparently healthy blood donor.

This work presents the second published report of an apparently healthy adult with an acquired B antigen. This case is unique because of the serial studies documenting the increase in strength of the B antigen, development of polyagglutinability, and absence of detectable gastrointestinal pathology. The cells of G.R., a 56-year-old caucasian female, came to our attention because of weak reactions with anti-B. Her cells were typed normal group A one year earlier. G.R.'s cells specifically absorbed an eluted anti-B. Her saliva contained A and H, but no B substance. The red cells were not polyagglutinable. Her cells did not react with the lectin Bandeiraea simplificolia. The cells reacted more strongly with anti-B from group A2 donors than A1. Her serum reacted with all normal group B cells, but was nonreactive with two other examples of acquired B cells. The autologous control and direct antiglobulin test were consistently negative. Samples examined three, six, and twelve months later showed the same serological results except that the acquired B antigen was stronger, although weaker than group B controls, and the cells were polyagglutinable. The cells failed to react with the following lectins Bandeiraea simplificolia I, Salvia sclarae, Salvia horminium and Soy bean lectin; but reacted with Arachis hypogea and Bandeiraea simplificolia II. Freezing and thawing the cells removed the polyagglutination but did not affect the B antigen. Normal A1 cells, but not O cells, became specifically agglutinable by anti-B after incubation with G.R.'s serum. G.R. is free from obvious pathology as determined by physical examination and gastrointestinal X-rays.

An example of a naturally occurring anti-cE (Rh27) that binds complement.

A serum sample from a nontransfused male containing anti-Rh27 and an additional weakly reacting antibody was investigated. One absorption of the serum with RZR1 cells left only anti-Rh27 while repeated absorption with R1R1 cells or autologous cells had no effect. Treatment of the serum with reducing agents destroyed all activity suggesting the antibody was predominantly IgM. Tests with monospecific antiglobulin reagents in the indirect antiglobulin test revealed very weak reactions with anti-IgM and anti-IgA, no reactions with anti-IgG, and strong reactions with anti-C3(C3c + C3d) and anti-C4. This is the first reported example of a naturally occurring complement binding anti-Rh27.

Neutrophil antibodies: detection and clinical application.

This paper discusses the current knowledge of neutrophil antibodies. Its purpose is fourfold: to review the antigens which have been found in neutrophils; to outline the major methodologies used to examine neutrophil antigen-antibody systems; to show the importance of neutrophil antibodies in immune neutropenia and febrile transfusion reactions; and to discuss the role of neutrophil antigens and antibodies in bone marrow and organ transplantation as well as in granulocyte transfusions.

The renal effect of intravenous adenine in humans.

The purine base, adenine, improves the posttransfusion viability of liquid stored blood. However, adenine in high doses may cause kidney damage becuase of the precipitation in renal tubules of its incoluble metabolite, 2,8-dioxyadenine. Adenine is not licensed for use in the United States because it may be nephrotoxic. In a controlled, randomized, double-blind study, eight human subjects received 10 mg/kg of adenine infused intravenously over one hour, four subjects received 5 mg/kg, and four subjects received no adenine. Renal function tests were performed on each subject before adenine infusion and one day and one week following the infusion. Tests included an assessment of glomerular function (serum creatinine, creatinine clearance, protein excretion), proximal tubular function (amino acid and glucose excretion), and distal tubular function (maximal acidifying and concentrating ability). Plasma and urine levels of adenine and 2,8-dioxyadenine were measured. Renal function tests showed no evidence of kidney damage secondary to adenine.