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ID PMID Title PublicationDate abstract
1594889 Angiotensinogen in chronic liver disease. 1992 Feb The renin substrate angiotensinogen (AGT) belongs to a supergene family of proteins that also includes alpha 1-antitrypsin (AAT) and alpha 1-antichymotrypsin (ACT), acute-phase reactants with known serine proteinase inhibitory (serpin) function. AGT lacks a known inhibitory function but is an acute-phase reactant. In this study we have compared the plasma levels, as analysed by electroimmunoassay, of AGT with AAT in patients with different types of chronic liver disease. AAT levels are regularly elevated in liver disease patients in contrast to AGT, which remains normal until late in the disease course. The AGT levels (mean +/- SD) were: in alcoholic cirrhosis (n = 19) 100 +/- 27.3%, in chronic active hepatitis (n = 14) 100 +/- 23.2%, in primary biliary cirrhosis (n = 18) 106 +/- 26.1% and in non-alcoholic cirrhosis (n = 15) 92 +/- 38.4%. Only occasionally were levels less than 50% of normal seen. In general, AGT levels were unrelated to sex and type of underlying liver disease and did not correlate with degree of hepatocellular impairment. Crossed immunoelectrophoresis showed no abnormal charge heterogeneity of AGT in patients with low levels. Our data are consistent with a dissociate expression of the homologous serpin genes in chronic liver disease. We speculate that the magnitude of the dissociated response is influenced by hormonal factors.
1551940 Interleukin 4 inhibits polyclonal immunoglobulin secretion and cytokine production by peri 1992 Jan Rheumatoid arthritis (RA) is associated with T- and B-cell dysfunction. Immunoglobulin (Ig) production is under the control of T cells and their derived cytokines such as interleukin 2 (IL-2) and IL-4. Herein we studied the regulation of the production of immunoglobulins and cytokines by peripheral blood mononuclear cells from RA patients and controls. In the controls, IL-4 inhibited Ig production in response to Staphylococcus aureus and pokeweed mitogen stimulation. IL-2 induced maximal Ig production in association with Staphylococcus aureus, whereas it inhibited pokeweed mitogen-induced production. In patients, levels of Ig production in response to mitogens and cytokines were reduced, particularly for the response to IL 2. The inhibitory effect of IL-4 on mitogen-induced Ig production was observed in RA patients as in the controls. Spontaneous production of IL-6 was increased in RA patients. These levels were correlated with indicators of active disease such as sedimentation rate and Ritchie index. IL-4 inhibited the production of IL-6, IL-1 beta, and tumor necrosis factor alpha (TNF alpha) by both controls and rheumatoid patients. Thus as first described for the T-cell response, mononuclear cells from RA patients display a reduced response to mitogens and cytokines which induce their B-cell differentiation into Ig-screening cells. However, IL-4 was able to inhibit Ig and cytokine production, properties suggesting a potential antiinflammatory role for this cytokine.
7882553 Analysis of proteins that interact with the IL-2 regulatory region in patients with rheuma 1995 Mar In order to investigate transcriptional regulation of lymphokine genes in rheumatic diseases, peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) were analysed for expression of DNA-binding proteins. Nuclear extracts prepared from unstimulated and mitogen-activated cells were studied for their ability to bind to 32P-labelled oligonucleotides containing the AP-1, NF-AT, NF-B and CD28RC sites of the IL-2 promoter. Using gel mobility-shift assay, detection of protein binding to the AP-1 site was reduced in SLE compared with controls. NF-AT binding activity was enhanced in all groups of patients, and was associated with measures of disease activity in RA. In addition, SSc patients showed increased NF-kappa B binding activity. Altered patterns of DNA-binding proteins suggest disturbed intracellular signalling which may contribute to abnormal lymphokine production in rheumatic diseases.
1349568 Polymerase chain reaction-based genotyping for allotypic markers of immunoglobulin kappa s 1992 May Allotypic markers of immunoglobulin kappa (Km) may be determined using a novel method of amplification of the constant segment (C kappa) (IGKC) by polymerase chain reaction (PCR) followed by restriction enzyme digestion. Restriction sites in the C kappa PCR product correlate with allotypic differences among Km(1), Km(1,2), and Km(3) alleles. An AccI site in the PCR product correlates with Km(3); and presence or absence of a MaeII site correlates with the Km(1) or Km(1,2) allele, respectively. Km allelic frequencies were determined in a Caucasian population and compared to genotypic frequencies of nearby polymorphic markers. Among unrelated individuals with rheumatoid arthritis (RA) and controls, there is no evidence of allelic association between CD8A and polymorphic markers of the immunoglobulin kappa region [a V kappa (IGKV) BglII polymorphism about 24 kb centromeric to C kappa, Km allotype, and a SacI polymorphism 3.5 kb telomeric to the C kappa segment]. Similarly, there is no allelic association of the SacI C kappa polymorphism with Km or with the BglII V kappa polymorphism. However, there is evidence of allelic association of V kappa B3 and Km, specifically between the V kappa BglII 2.2-kb allele and Km(3) and also between the V kappa 3.5-kb allele and Km(1,2). Therefore, Km typing by PCR-based methods suggests the presence of allelic association between polymorphisms within the coding region of the C kappa segment and the nearest V kappa segment.
7986741 Subcutaneous palisading granuloma of the scalp in childhood. 1994 Subcutaneous palisading granulomas, lesions characterized by collagen necrosis and chronic inflammatory changes, may present as ill-defined, immobile, nontender masses of the scalp. They are frequently multiple and may vary in size over time. Imaging studies rarely show involvement of the calvarium. The histological pattern of palisading histiocytes around necrobiotic granulomas is seen in association with a variety of systemic illnesses but more commonly occurs as an isolated entity in childhood. They are unlikely to herald rheumatological disease unless the erythrocyte sedimentation rate is elevated. In the presence of juvenile rheumatoid arthritis, histological confirmation is usually not indicated. If the lesions are not associated with any other clinical symptoms excisional biopsy may be indicated to establish a diagnosis. The nodules need not be removed as they will spontaneously regress.
7710608 [More precise characterization of humoral immune reactivity to cartilage tissue in patient 1995 Feb The problems with repeated failure of cartilage grafting in reconstructive surgery are not yet resolved. Humoral immunoreactivity against chondrocytes as well as typical cartilage collagens type II, IX and XI was investigated in patients who showed resorptions and/or rejections of transplanted cartilage grafts. The presence of antibodies against isolated human chondrocytes was determined using an indirect immunofluorescence method, an enzyme-linked immunosorbent assay (ELISA) for chondrocytes and immunoblotting with chondrocyte cell membranes. Furthermore, an ELISA for collagens type II, IX and XI as well as immunoblotting with purified collagens type II and XI were used. The control groups consisted of patients with successful cartilage transplantation, patients suffering from rheumatoid arthritis and healthy persons. Patients with unsuccessful cartilage transplantation showed significantly elevated titres of antibodies against chondrocytes (p < 0.001) and collagens type IX and XI (p < 0.001) compared to the control groups. In one patient with unsuccessful cartilage graft, we could also find a humoral reactivity against collagen type XI by immunoblotting. In contrast, no humoral immune reactivity was demonstrable against chondrocyte cell membranes by immunoblotting. In all examined patients fifty percent of patients with repeated resorptions or rejections of transplanted grafts showed antinuclear antibodies (ANA), demonstrating a possible but not yet declared autoimmune disease. These data confirm a humoral immunoreactivity against chondrocytes as well as against collagen which could be responsible for resorptions and/or rejections observed after cartilage graft.
7916590 Generation and molecular analyses of two rheumatoid synovial fluid-derived IgG rheumatoid 1993 Jul OBJECTIVE: To study the Ig genes that encode IgG rheumatoid factor (IgG-RF) from rheumatoid synovial fluid. METHODS: We used rheumatoid synovial fluid B cells to generate IgG-RF-secreting hybridomas. We then characterized their binding properties and determined their nucleotide sequences. RESULTS: Two monospecific IgG-RFs were obtained. Sequence analysis of the RFs revealed a new V lambda gene family (designated V lambda 9) and extensive somatic diversification, including a duplication-insertion of 18 nucleotides (6 amino acid residues) into a hypervariable region. CONCLUSION: The data provide further support for an antigen-driven response in the sustained production of potentially pathogenic IgG-RFs in rheumatoid synovium.
8573146 Fas antigen expression on synovial cells was down-regulated by interleukin 1 beta. 1996 Jan 5 Recent reports revealed that Fas antigen is functionally expressed on human synovial cells and apoptosis can be induced in these cells by anti-Fas antibody. We examined the effect of interleukin 1 beta (IL-1 beta) on Fas antigen-mediated apoptosis on human synovial cells in vitro. Using flowcytometric analysis, IL-1 beta inhibited Fas antigen expression on synovial cells in a dose-dependent fashion. No significant difference of Fas antigen gene expression between IL-1 beta-treated and untreated synovial cells was observed by RT-PCR analysis, suggesting that the inhibitory effect of Fas antigen expression by IL-1 beta is at posttranscriptional level. Apoptosis of synovial cells was easily induced by treatment of these cells with anti-Fas antibody. In contrast, pretreatment of synovial cells with IL-1 beta protected these cells against Fas antigen-mediated apoptosis. The expression of bcl-2 on synovial cells, known to interfere with the apoptotic process mediated by the Fas antigen, was not influenced by IL-1 beta. Our results suggest that IL-1 beta inhibits Fas antigen-mediated apoptosis of synovial cells and may perpetuate the hyperplasia of the synovium in patients with rheumatoid arthritis.
1623598 Serum adenosine deaminase: isoenzymes and diagnostic application. 1992 Jul Human adenosine deaminase (ADA; EC 3.5.4.4) consists of three isoenzymes: ADA1, ADA1+CP, and ADA2. We developed an electrophoretic technique to distinguish between these three isoenzymes. The isoenzyme pattern was studied in tissue and cell homogenates, as well as in serum from normal subjects and from patients with increased serum ADA who had either hepatitis, infectious mononucleosis, tuberculosis, pneumonia, rheumatoid arthritis, or acute lymphoblastic leukemia (ALL). The highest ADA activity was found in lymphocytes and monocytes. ADA2 could be detected only in monocytes (18% of total ADA activity). It was also the predominant isoenzyme in the sera of controls and all disease groups, except for ALL--the only condition evaluated that is not of an inflammatory nature. We conclude that serum ADA reflects monocyte/macrophage activity or turnover in most diseases studied. The exception is ALL, where serum ADA most probably originates from lymphocyte precursors.
1535472 HIV infection and rheumatic diseases--autoimmune mechanisms in immunodeficient hosts. 1992 Mar The recognition of a newly acquired immunodeficiency syndrome (AIDS) in 1981 has had dramatic social and economic implications. Eventually, an epidemic of the viral infection developed with a potential to spread globally. The extraordinary breadth of AIDS research lead to the early identification of the causative agent: The human immunodeficiency virus (HIV) is a member of the lentivirus family and is characterized by its ability to remain latent within the genome of the infected host. The primary targets for the HIV are helper T-lymphocytes and monocytes/macrophages, which results in the progressive destruction of immune functions in the infected hosts. Binding to and entry into the cells is facilitated by a high-affinity interaction of a viral glycoprotein and the CD4 molecule. Signs of the immunodeficient state, manifested as a broad spectrum of opportunistic infections initially dominated the clinical presentations of HIV infected patients. Over the last decade, however, the manifestations of HIV infection have steadily grown and, surprisingly, include many rheumatic syndromes and autoimmune phenomena. The finding that HIV-infected individuals present with a highly progressive form of Reiter's syndrome and psoriasis has challenged our understanding of immune functions in HLA-B27 associated disorders. Obviously, CD8+ T-cells can maintain function despite the depletion of CD4+ helper T-cells. Consistent with the current model of the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus, patients with these syndromes were described to go into remission when CD4+ T-cells were selectively depleted in active HIV infection. There is growing evidence that complex mechanisms arise from the interaction of the HIV and the human host which extend beyond the initial expectation that the virus only kills CD4+ helper T-cells. Indicating yet another aspect of HIV disease, a new syndrome mimicking Sjögren's syndrome has been encountered in HIV-infected patients and has been named the diffuse infiltrative lymphocytosis syndrome. Dense infiltrates of CD8+, potentially antiviral killer cells, are characteristically found in the salivary glands of patients who express a certain HLA genotype and who are, typically, long-term survivors of the disease. Recent reports have stressed a new mechanism of disease induction in HIV infected patients. Inappropriate induction of potentially destructive cytokines appears to be initiated by the viral infection and the expression of the viral genome seems to be effectively modulated by cytokines. In summary, HIV infection may provide important insights in the pathogenesis of rheumatic diseases co-occurring with HIV infections.(ABSTRACT TRUNCATED AT 400 WORDS)
7763112 CD4 T cells in the rheumatoid joint are oligoclonally activated and change during the cour 1995 Apr OBJECTIVE: To assess the nature of T cell receptor (TCR) utilisation by CD4 T cells in the rheumatoid joint. METHODS: Sequencing of the joining (NDJ) region of TCR beta chain mRNA isolated from synovial fluid CD4 T cells was performed in three patients in order to determine if oligoclonal expansion of particular sequences was present. Two patients were studied longitudinally to determine if these sequences changed over time. RESULTS: A number of dominant clonotypes were found within the TCR transcripts sequenced in each patient. In the two patients who were studied longitudinally, different dominant clonotypes were detected over time. No single clonotype was persistently dominant during the period of study. CONCLUSIONS: The pattern of TCR usage showed multiple oligoclonally expanded CD4 T cells within the rheumatoid joint. The change in clonotypes within the joint over time suggests that different antigens may be able to elicit synovial inflammation during the course of rheumatoid disease.
8403583 D-penicillamine induced myasthenia gravis: clinical, serological and genetic findings. 1993 Jul Eight cases of D-penicillamine (DP) induced myasthenia gravis (MG) are presented. Seven patients were being treated for rheumatoid arthritis (RA) and one for scleroderma. The mean duration of DP treatment until the myasthenic symptoms developed ranged from 2-8 months. The DP dose reached 500 mg daily. It was found that the clinical and immunological findings were almost similar to those of idiopathic MG, but were less severe. All patients had increased titers of acetylcholine receptor antibodies in their sera. Discontinuation of D-penicillamine resulted in the complete resolution of myasthenic symptoms after 2-6 months. One patient required ventilation, immunosuppressive therapy and plasma exchange. No association was found between DP related MG and the various autoantibodies tested. Immunogenetic analysis showed that three patients had HLA-DR1, two HLA-DR3, one HLA-DR4 and one HLA-DR5. In conclusion, the clinical presentation of DP-induced MG seems similar to idiopathic MG. DP-related MG is relatively benign, although it sometimes can cause life-threatening muscle weakness requiring aggressive therapy. The relatively small number of patients included in this study, however, does not permit any firm conclusions regarding the HLA associations of DP-related MG.
1279171 Tenascin and fibronectin distribution in human normal and pathological synovium. 1992 Sep Tenascin is a glycoprotein found mainly in the extracellular matrix of developing and malignant tissues. The distribution of this molecule in normal and pathological synovia from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) was investigated by indirect immunofluorescence utilizing specific monoclonal antibodies. The same technique was used to study total fibronectin (tFn) in synovial tissues as well as ED-A and ED-B containing fibronectin (Fn) isoforms (A-Fn, B-Fn), generated by alternative splicing of pre-mRNA. Tenascin was found in normal synovium just beneath the whole lining cell layer. However, a higher density and spreading pattern of distribution was observed in OA and RA sections. A-Fn and B-Fn isoforms were prominent and widespread throughout the normal synovial lining; in hypercellular synovial lining (in RA and OA samples), A-Fn and B-Fn were also observed spreading in the sublining, as well as tFn.
1613698 Life table analysis of 879 treatment episodes with slow acting antirheumatic drugs in comm 1992 May In 596 patients with RA managed over a decade in a community practice setting, 879 slow acting antirheumatic drug (SAARD) treatment episodes were analyzed using 5-year life tables. The probability of continuation of therapy was 50% by 9-24 months for all drugs except for methotrexate (MTX), which was 62% by 5 years [corrected]. MTX treatments were of significantly longer duration than those of all other SAARD (p less than 0.001); terminations for both inefficacy (p less than 0.001) and toxicity (NS) were less likely. These findings concur with recent evidence suggesting that MTX is a superior SAARD in this setting.
7822808 Balance of IL-1 receptor antagonist/IL-1 beta in rheumatoid synovium and its regulation by 1995 Feb 1 The spontaneous production of IL-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1Ra) by rheumatoid arthritis (RA) synovium, and the regulation of their production by IL-4 and IL-10, were studied. Supernatants from cultured synovium pieces from 19 RA patients were assayed for IL-1 beta and IL-1Ra production using ELISA and RIA, respectively. After 10 days of culture, spontaneous production of IL-1Ra was 1.42 +/- 0.43 ng/ml/100 mg of synovium whereas spontaneous production of IL-1 beta was 4.03 +/- 0.90 ng/ml/100 mg of synovium (n = 19). The addition of IL-4 reduced IL-1 beta production by 2.3-fold (p = 0.001) and increased that of IL-1Ra by 2.8-fold (p = 0.003). IL-10 had no significant effect on IL-1Ra production and suppressed IL-1 beta production (primarily in samples producing high levels of IL-1 beta). However, IL-10 was less potent than IL-4 in suppressing IL-1 beta production. IL-1Ra was mainly produced by rheumatoid synovial monocytes/macrophages. IL-4 was more potent than IL-10 in inducing IL-1Ra production by monocytes/macrophages purified from RA synovium, as well as from RA blood. Thus, RA synovium is characterized by an imbalance between IL-1Ra and IL-1 beta production, in favor of the latter. IL-4, and to a lesser extent IL-10, shift this balance in favor of an anti-inflammatory situation.
8624638 Anterior pituitary function in patients with newly diagnosed rheumatoid arthritis. 1996 Apr Hormonal dysfunction involving the hypothalamic-pituitary-adrenal (HPA) axis, prolactin (PRL) secretion and sex hormone status has been supposed to contribute to the development or persistence of rheumatoid arthritis (RA). In addition, a reduced number of glucocorticoid receptors on circulating lymphocytes has been found in patients with RA. However, so far most studies have been performed in pre-treated patients. A combined test for total anterior pituitary reserve was performed in 10 patients with newly diagnosed untreated RA. Before and after stimulation with the respective hypothalamic releasing hormones, RA patients showed no difference in plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol, prolactin (PRL) and thyroid-stimulating hormone (TSH) when compared to healthy controls. In contrast, the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) was blunted in RA patients. The hypothalamic-pituitary-thyroid/gonadal and adrenal axes seem to be unaltered in RA. However, if one considers the presence of chronic inflammation, normal plasma ACTH and cortisol concentrations must be considered as inappropriately low. The observed blunted GH release could be mediated by cytokines (e.g. IL-1), which are known to be elevated in RA.
1386877 Human neutrophils produce high levels of the interleukin 1 receptor antagonist in response 1992 Aug 1 Neutrophils, an abundant cell type at sites of inflammation, have the ability to produce a number of cytokines, including interleukin 1 (IL-1), IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-alpha). In this study, we have examined the ability of human neutrophils to produce the IL-1 receptor antagonist (IL-1Ra), a 17-23-kD protein recently isolated and cloned from macrophages. Since IL-1Ra has been shown to inhibit both the in vitro and in vivo effects of IL-1, its production by large numbers of tissue-invading neutrophils might provide a mechanism by which the effects of IL-1 are regulated in inflammation. Using antibodies that are specific for IL-1Ra and a cDNA probe encoding for this protein, we were able to show that neutrophils constitutively produce IL-1Ra. However, after activation by GM-CSF and TNF-alpha, IL-1Ra was secreted into the extracellular milieu where it constituted the major de novo synthesized product of activated neutrophils. None of a large array of other potent neutrophil agonists were found to affect the production of IL-1Ra by neutrophils. Quantitative measurements by enzyme-linked immunosorbent assay revealed that intracellular IL-1Ra is in eightfold excess of the amount secreted in supernatants when studying nonactivated neutrophils. However, in GM-CSF- and TNF-alpha-activated cells, this difference was reduced to values between four- and fivefold, as virtually all of the de novo synthesized IL-1Ra was secreted. In activated cells, the intracellular content of IL-1Ra was found to be in the 2-2.5-ng/ml range per 10(6) neutrophils, whereas levels reached the 0.5-ng/ml range in supernatants. This would imply that IL-1Ra is produced in excess of IL-1 by a factor of at least 100, an observation that is in agreement with the reported amounts of IL-1Ra needed to inhibit the proinflammatory effects of IL-1. Neutrophils isolated from an inflammatory milieu, the synovial fluid of patients with rheumatoid arthritis, were found to respond to GM-CSF and TNF-alpha in terms of IL-1Ra synthesis, indicating that the in vitro observations made in this study are likely to occur in an inflammatory setting in vivo.
8055201 Is serum transferrin receptor useful for detecting iron-deficiency in anaemic patients wit 1994 Aug We investigated whether determination of serum transferrin receptor (TfR) is useful for detecting iron-deficiency in patients with chronic inflammatory diseases and for differentiating between iron-deficiency anaemia and anaemia of inflammation. Using an immunofluorometric assay, serum TfR was measured in 34 anaemic patients. Of these patients, 23 had a chronic rheumatic disease, 13 with both inflammation and iron-deficiency and 10 with anaemia of inflammation only; the other 11 patients had iron-deficiency anaemia and no evidence of inflammation. Serum TfR concentrations were lower in patients with anaemia of inflammation (2.6 +/- 0.2 mg/l, mean +/- S.E.M.) than in patients with iron-deficiency anaemia (6.7 +/- 1.1 mg/l, P < 0.01) or those with both inflammation and iron deficiency (5.8 +/- 1.0 mg/l, P < 0.01). Among patients with inflammatory disease, correlations between TfR and ferritin concentrations (r = -0.62, P < 0.05) and TfR and erythropoietin concentrations (r = 0.69, P < 0.001) were observed in iron-deficient subjects only. TfR, though not superior to serum ferritin, can help to distinguish between anaemia of inflammation and iron-deficiency anaemia and to identify iron-deficiency in subjects with chronic inflammation.
8059523 [The human herpesvirus type 6 (HHV-6) and its spread in Russia]. 1993 Mar This is the first presentation of information on the circulation of human herpes virus type 6 (HHV-6) in the population of the mid-European part of this country. The results of the study indicate that HHV-6 is widely spread both among apparently normal people and among patients with different pathologies. The studies using immunofluorescence test showed that the percentage of HHV-6-infected subjects was practically similar among blood donors, patients with nasopharyngeal cancer, rheumatoid arthritis, hemophilia, and patients with transplanted kidney, varying from 34% to 49%. A significantly higher per cent (66%) and higher antibody titres to HHV-6 were detected in sera from patients with hemoblastoses. A high level of HHV-6 infection among patients with hemoblastoses was also confirmed by the results of immunoblotting showing a wider spectrum and higher intensity of the detectable proteins. It should be noted that the amounts of virus-specific proteins detectable by some sera showed individual variations indicating different levels of expression of viral proteins in different individuals.
8277357 Detection of antineutrophil autoantibodies by flow cytometry: use of unfixed neutrophils a 1993 Antineutrophil antibodies may be found in the sera of patients with chronic neutropenia as well as in the sera of a variety of patients with neutropenia and associated autoimmune or infectious disorders. We evaluated an immunofluorescent flow cytometric technique for the measurement of antineutrophil antibodies in serum. Sera from patients with suspected immune neutropenia were studied and compared with a group of sera from normal healthy individuals, as well as with sera from patients with rheumatoid arthritis and systemic lupus erythematosus. Of 159 patients with suspected immune neutropenia and a variety of associated clinical disorders, 59 (37%) were found to have evidence for enhanced binding of IgG to normal target neutrophils, interpreted as positive for antineutrophil antibodies. Whereas 0/37 non-neutropenic patients with typical RA had positive results, 51/244 (21%) of sera from nonneutropenic patients with SLE or other collagen vascular disorders showed enhanced IgG binding to neutrophils. Living neutrophils were used to study the effects of cellular activation, and increased antibody binding was observed with certain sera that contained IgG directed against activation-dependent antigens. We found that, under controlled conditions, flow cytometry can be reliably used to detect antineutrophil autoantibodies, with unfixed, living neutrophils as antigenic targets.