Serum IgA anti-gliadin antibodies in an adult population sample

IgA-class anti-gliadin antibodies (AGA) and IgA-, IgG-, IgM-class anti-reticulin antibodies (ARA) were determined in 1461 persons, representing 84% of a population from the village of Karksi-Nuia. AGA were detected by enzyme-linked immunosorbent assay (ELISA) and ARA by indirect immunofluorescence. Fifty-two (3.5%) persons had IgA-class AGA, of whom 48 and an additional three of four persons with diarrhea were biopsied. All biopsies showed normal small intestinal mucosal architecture. All 1461 persons were negative for ARA. Our results demonstrate that AGA are frequently detected in an adult Estonian population and positivity increases with age in persons with normal small intestinal mucosa. Positivity for AGA does not predict silent undetected celiac disease but rather represents a normal response to dietary antigens in the elderly. Inability to detect ARA suggests that celiac disease does not exist in this population. As none of the AGA-positive but ARA-negative biopsied persons had celiac disease, ARA might be a more specific serologic marker for celiac disease than AGA.Supported by a grant from the Ministry of Health, Estonia. Dr. Oivi Uibo was also supported by a grant from the Emil Aaltonen Foundation.     

HTLV-III infection after bone marrow transplantation

We prospectively documented the development of a fatal, secondarily acquired severe immunodeficiency in a 19-year-old man who underwent uncomplicated bone marrow transplantation. He had no graft v host disease (GVHD) and had normal recovery of his immune system as determined by lymphocyte phenotyping, mitogenic responses of his peripheral blood lymphocytes, and his ability to secrete immunoglobulin. This alteration in immunity was associated with the acquisition of antibody to HTLV-III. His only risk factor for the development of HTLV-III infection was the transfusions he had received during the transplant and recovery period. Two of his 54 transfusions were from an asymptomatic individual at high risk for acquired immunodeficiency syndrome (AIDS), who was subsequently found to be seropositive for anti-HTLV-III and from whom HTLV-III was isolated. The loss of immunocompetence in patients without chronic GVHD disease is unusual, and our data support the view that this patient's immunodeficiency was due to HTLV-III. When bone marrow transplant recipients without chronic GVHD develop late opportunistic infections, consideration should be given to transfusion-associated AIDS.     

Identification of a distinct low-affinity receptor for human interleukin-4 on pre-B cells

Biotinylated interleukin-4 (IL-4) was used to examine IL-4 receptor (IL- 4R) expression on a range of human B-cell lines by flow cytometry. Using high concentrations of biotinylated IL-4, we have identified a novel low-affinity IL-4 receptor expressed at high levels on pre-B lines. Expression of this low-affinity receptor did not correlate with detected mRNA levels for the previously cloned receptor or with reactivity of two anti-human IL-4R monoclonal antibodies (MoAb). Radiolabeled IL-4 cross-linking studies using pre-B lines showed a doublet of 65 to 75 Kd in contrast to the 110- to 130-Kd molecule detected on cells expressing the cloned IL-4R. A soluble IL-4 binding protein (IL-4bp) was purified from the supernatants of three pre-B lines expressing the low-affinity receptor on their surface. IL-4bp could block both IL-4-mediated CD23 induction on tonsil B cells and IL- 4-induced inhibition of proliferation of the pre-B line JM1. Partial N- terminal amino acid sequence was obtained from purified IL-4bp that confirmed this protein to be novel. A 12 amino acid peptide based on the IL-4bp sequence was used to produce a polyclonal antiserum that was reactive with purified IL-4bp, and also bound to the surface of pre-B cells but not to murine CTLL cells transfected with the human IL-4R. Blocking MoAb against the previously characterized high-affinity receptor inhibited IL-4-mediated proliferation of hIL-4R+ CTLL cells but had no effect on IL-4-induced inhibition of JM1 cell proliferation, and only partially inhibited IL-4-mediated CD23 and sIgM induction and proliferation of tonsil B cells. The data presented here provide evidence for a novel cell-surface expressed low-affinity IL-4R that also exists as a biologically active soluble IL-4 binding protein.     

Marrow transplantation for acute lymphoblastic leukemia: factors affecting relapse and survival

Transplant outcome was analyzed in 690 recipients of bone marrow transplants (BMTs) for acute lymphoblastic leukemia (ALL) in first (n = 299) or second remission (n = 391). Actuarial 5-year leukemia-free survival was 42% +/- 9% (95% confidence interval) and 26% +/- 6%, respectively; relapse rates were 29% +/- 9% and 52% +/- 8%, respectively. Five-year leukemia-free survival was 56% +/- 18% in children and 39% +/- 10% in adults (P less than .02) transplanted in first remission. In first-remission adults, non-T-cell phenotype, male to female donor-recipient sex-match and graft-v-host disease (GVHD) were associated with decreased leukemia-free survival; inclusion of corticosteroids in the regimen to prevent GVHD was associated with increased leukemia-free survival. Variables associated with decreased leukemia-free survival after second-remission transplants were age greater than or equal to 16 years and relapse occurring while on therapy. Variables associated with increased probability of relapse were similar for first- and second-remission transplants and included GVHD prophylaxis without methotrexate and absence of GVHD. In first- remission transplants, leukocyte count greater than or equal to 50 x 10(9)/L at diagnosis was also associated with increased relapse; in second remission, relapse while receiving chemotherapy was also associated with increased posttransplant relapse. These data emphasize the importance of both disease- and transplant-related variables in predicting outcome after BMT. They may be used to explain differences between studies, design future trials, and identify persons most likely to benefit from BMT.     

Adhesion of malaria-infected red blood cells to chondroitin sulfate A under flow conditions

Adhesion of parasitized red blood cells (PRBCs) to microvascular endothelial cells (ECs) is a distinctive feature of Plasmodium falciparum malaria and is a central event in the development of life- threatening complications such as cerebral malaria. PRBCs adhere to several EC-expressed molecules in vitro, but the relative importance of these interactions in vivo remains unclear. Chondroitin sulfate A (CSA) is the most recent EC surface-associated molecule to be implicated in the adhesive process. Accordingly, we have studied adhesion of PRBCs to CSA in vitro using a parallel-plate flow chamber. Under controlled flow conditions, PRBCs adhered to CSA in a concentration-dependent manner at wall-shear stresses up to 0.2 Pa, a value that is within the physiological range for venules. Once adhered, PRBCs remained stationary (rather than rolling) and continued to remain stationary even when the wall-shear stress was raised to supravenular levels. The adhesive interaction was strong and a proportion of adherent PRBCs could withstand detachment at stresses up to 2.5 Pa. Soluble CSA at pharmacological concentrations prevented adhesion of flowing PRBCs in a concentration-dependent manner but failed to reverse established adhesion. Adhesion of PRBCs to CSA could contribute to the pathogenesis of malaria, and soluble CSA may have a useful therapeutic effect.     

Excessive Aluminum Accumulation in the Bones of Patients on Long‐Term Parenteral Nutrition

Background: Aluminum (Al) contamination of parenteral nutrition (PN) solutions remains a concern for long‐term PN patients. Al accumulates particularly in bone. Excessive exposure to Al may result in increased Al body burden and impaired bone formation and mineralization, leading to bone disease. Although the U.S. Food and Drug Administration (FDA) has limited Al contamination in large‐volume parenteral solutions, small‐volume parenterals may still contribute considerable amounts of Al to PN solutions. The goal of this study is to determine whether or not long‐term adult PN patients remain at risk for increased bone Al accumulation. Methods: We measured Al accumulation in autopsy bones from 7 patients who had received PN for 2–21 years and compared bone Al levels with those in living control patients undergoing hip or knee replacement. Electrothermal atomic absorption spectrometry was used for bone Al measurements. Results: When compared with bone Al content in controls, markedly elevated Al levels (P < .0001) were found in the bones of all but 1 patient, who received PN for only 2 years before death. Even greater Al accumulation was found for PN patients who developed late renal impairment (P = .0159). Conclusions: We conclude that long‐term adult PN patients continue to be at risk for Al toxicity.