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Background Vaccination is a promising strategy to protect vulnerable groups like immunocompromised inflammatory bowel disease [IBD] patients from an infection with SARS-CoV-2. These patients may have lower immune responses. Little is known about the cellular and humoral immune response after a SARS-CoV-2 vaccination in IBD patients. Methods Totals of 28 patients with IBD and 27 age- and sex-matched healthy controls were recruited at Jena University Hospital. Blood samples were taken before, after the first, and in a subgroup of 11 patients after second dose of a SARS-CoV-2 vaccination. Cellular immune response, including IFN-γ and TNF-α response and antibody titres, were analysed. Results Overall, 71.4% of the IBD patients and 85.2% of the controls showed levels of anti-SARS-CoV-2 antibodies above the cutoff of 33.8 BAU/ml [p = 0.329] after the first dose. Even in the absence of SARS-CoV-2 antibodies, IBD patients showed significant T cell responses after first SARS-CoV-2 vaccination compared with healthy controls, which was not influenced by different immunosuppressive regimens. Associated with the vaccination, we could also detect a slight increase of the TNF production among SARS-CoV-2-reactive TH cells in healthy donorsn [HD] and IBD patients. After the second dose of vaccination, in IBD patients a further increase of humoral immune response in all but one patient was observed. Conclusions Already after the first dose of a SARS-CoV-2 vaccination, cellular immune response in IBD patients is comparable to controls, indicating a similar efficacy. However, close monitoring of long-term immunity in these patients should be considered.

The research consortium Neuroimmunology and Pain (Neuroimpa) explores the importance of the relationships between the immune system and the nervous system in musculoskeletal diseases for the generation of pain and for the course of fracture healing and arthritis.The spectrum of methods includes analyses at the single cell level, in vivo models of arthritis and fracture healing, imaging studies on brain function in animals and humans and analysis of data from patients.Proinflammatory cytokines significantly contribute to the generation of joint pain through neuronal cytokine receptors. Immune cells release opioid peptides which activate opioid receptors at peripheral nociceptors and thereby evoke hypoalgesia. The formation of new bone after fractures is significantly supported by the nervous system. The sympathetic nervous system promotes the development of immune-mediated arthritis. The studies show a significant analgesic potential of the neutralization of proinflammatory cytokines and of opioids which selectively inhibit peripheral neurons. Furthermore, they show that the modulation of neuronal mechanisms can beneficially influence the course of musculoskeletal diseases.Interventions in the interactions between the immune system and the nervous system hold a great therapeutic potential for the treatment of musculoskeletal diseases and pain.

Hintergrund Regulatorische T-Zellen (Treg) sind essenziell fur die Aufrechterhaltung der immunologischen Selbsttoleranz, indem sie die Aktivierung und Expansion autoreaktiver Zellen kontrollieren. Sie tragen daher entscheidend zur Verhinderung und Kontrolle von Autoimmunerkrankungen bei.

Tim-3 has opposing roles in innate and adaptive immunities. It not only dampens CD4+ and CD8+ T cells responses but also enhances the ability of macrophages to eliminate intracellular pathogens. After peroral infection with 100 cysts of Toxoplasma gondii genetically susceptible C57BL/6 mice develop an unchecked Th1 response associated with the development of small intestinal immunopathology. Here we report that upon infection with T. gondii, both susceptible C57BL/6 and resistant BALB/c mice exhibit increased frequencies of Tim-3+ cells in spleens and mesenteric lymph nodes. The number of Tim-3+ cells was significantly higher in C57BL/6 than in BALB/c mice. Tim-3 was expressed by macrophages, dendritic, natural killer, as well as CD4+ and CD8+ T cells. Highest frequencies of Tim-3+ cells were observed at the peak of Th1 responses (day 7 post infection) concurrent with the development of ileal immunopathology. Infected Tim-3-deficient BALB/c mice did not develop ileal immunopathology nor did their parasite loads differ from those in wildtype BALB/c mice. Thus, although Tim-3 is markedly upregulated upon infection and differentially regulated in susceptible and resistant mice upon infection with T. gondii, the absence of Tim-3 is not sufficient to overcome the genetic resistance of BALB/c mice to the development of Th1-driven small intestinal immunopathology.

Objectives Pressure ulcers impose a major lifetime medical problem to patients with high-grade spinal cord injury (SCI). For patients with stages 3-4 pressure ulcers, plastic surgery is often the only remaining treatment option. Despite considerable flap failure rates of around 30%, only sparse knowledge exists on predictors for flap failure. Hence, identification of predictors for flap failures is needed. Methods We prospectively enrolled 38 SCI patients with stages 3-4 pressure ulcers scheduled for plastic surgery. Preoperative wound swabs, intraoperative tissue samples and postoperative drainage liquids were microbiologically analyzed. In multivariable logistic regression analyses, bacterial loads of deep tissue cultures of intraoperative samples as well as other clinical variables were analyzed with respect to the prediction of flap failures. Results The flap failure rate was 27.5%. Bacterial loads of deep tissue cultures were not predictive for flap failure, neither was the colonization with a specific bacterial strain. We observed a considerable fluctuation of microbiological environment from initial swab cultures, intraoperative samples and postoperative drainage fluids. Antibioprophylaxis was sufficient in only 75% of deep tissue cultures and 69% of drainage fluids. Insufficient antibioprophylaxis was associated with a higher flap failure rates (odds ratio 6.3, confidence interval 1.2-41.0). Conclusion After inpatient wound conditioning, bacterial load analysis of intraoperative wound tissue cultures is ineffective in order to predict flap failure rates in SCI patients with stages 3-4 pressure ulcers after flap surgery. Instead, insufficient antibioprophylaxis might be a factor contributing to flap failure.

Regulatory T cells (Treg) are crucial for the maintenance of immunological peripheral tolerance by controlling the activation and expansion of autoreactive cells; therefore, they make a decisive contribution to the prevention and control of autoimmune diseases.The aims of this article are to summarize the history and role of Treg in science and medicine, to provide a brief introduction to the development and function, to explain how failures in Treg biology contribute to the development of autoimmune disease, to explain their specific role in particular rheumatic diseases and to provide an introduction to the therapeutic use of Treg in autoimmune diseases.Relevant original literature and review articles were analyzed and the results are summarized in this article.Disorders in Treg biology can contribute to the development of rheumatic diseases in various ways. In addition, their capability to suppress autoimmunity renders Treg an attractive target for the treatment of rheumatic diseases.The concept of Treg-mediated immunoregulation has evolved into an independent field of research in immunology and medicine. First translational approaches and clinical studies confirmed the therapeutic efficacy of Treg in the treatment of autoimmune syndromes.

Das BMBF-geforderte Konsortium IMPAM untersucht in 10 Projekten, koordiniert vom DRFZ Berlin und dem Universitatsklinikum Jena, den molekularen Dialog zwischen immunologischen Gedachtniszellen und mesenchymalen Zellen bei chronisch entzundlichen Gelenkerkrankungen wie der rheumatoiden Arthritis und der ankylosierenden Spondylitis. Ziel ist es, so therapeutisch in diese Interaktionen einzugreifen, dass das pathogene Imprinting der proinflammatorischen Gedachtniszellen geloscht und gleichzeitig die antiinflammatorische Kapazitat korpereigener regulatorischer Zellen bei den Patienten wiederhergestellt wird.

In an earlier study, we found that T-cell lines (TCL) from five patients with treatment-resistant Lyme arthritis preferentially recognized Borrelia burgdorferi outer surface protein A (OspA), but TCL from four patients with treatment-responsive arthritis only rarely recognized this protein. Dominant T-cell recognition of an arthritogenic OspA epitope is one way in which the immune response against OspA might be involved in the pathogenesis of treatment-resistant Lyme arthritis. In an effort to test this hypothesis, we mapped the epitopes of 31 OspA-specific TCL and five T-cell clones derived from the synovial fluid or peripheral blood samples of three patients with treatment-resistant Lyme arthritis. Although each patient's TCL recognized a broad array of OspA peptides with different individual patterns, two regions of OspA were dominantly recognized. Each patient's TCL dominantly recognized a C-terminal epitope of OspA, ranging from amino acids (aa) 214 to 233 in one patient to 244 to 263 in another, and the TCL of all three patients dominantly recognized an epitope between aa 84 and 113. These dominant regions were confirmed by clonal analysis in one patient. Thus, the region of OspA between aa 84 and 113 was the dominant T-cell epitope shared by these three patients with treatment-resistant Lyme arthritis. If the T-cell response to OspA is involved in the pathogenesis of treatment-resistant Lyme arthritis, and epitope contained within aa 84 to 113 is a potentially arthritogenic epitope.

Background and purpose Pressure sores are a major health problem in spinal cord injury (SCI). In this population pressure damage to peripheral nerves was not thoroughly investigated so far. However, intact peripheral nerves and innervated muscles are a prerequisite for the effectiveness of supportive therapies like functional electrical stimulation (FES). Methods We assessed electroneurographic (ENG) data of lower limbs in SCI individuals admitted to our hospital due to severe pressure sores. Our centers prospectively acquired ENG data of the European Multicenter study about SCI (EMSCI) patients served as early control. Results In the pressure sore cohort (n = 15) all patients were sensory-motor complete (American Spinal Cord Injury Association Impairment Scale A). Most patients (10/15) suffered from a severe axonal sensory-motor polyneuropathy in paralysed legs with absent compound muscle action potentials (CMAPs) of tibial/peroneal nerves as well as absent sensory nerve action potentials of sural nerves. The onset of this polyneuropathy dates within the first year after incident SCI and was mainly associated with increasing sensory-motor completeness as demonstrated by a significant CMAP drop of our centers EMSCI-ENG data on serial tibial nerve recordings in 275 patients. Conclusions Severe SCI is associated with an early-onset axonal polyneuropathy in paralysed limbs to which pressure damage might contribute. Because intact peripheral nerves are required for: (i) maintenance of motor function in centrally impaired muscles; and (ii) effectiveness of supportive therapies like FES, ENG-monitoring could serve as a low invasive screening method for peripheral nerve integrity in patients with SCI to initiate pressure relief procedures early enough.

The Research Consortium IMPAM (IMprinting of the PAthogenic Memory for rheumatic inflammation) has recently been funded by the Federal Ministry of Education and Research in Germany. Within this consortium ten different research groups, coordinated by the German Rheumatism Research Center (DRFZ) and the University Hospital Jena, will examine the molecular dialogue between immune system memory cells and mesenchymal cells in chronic rheumatic diseases, such as rheumatoid arthritis or ankylosing spondylitis. The consortium's aim is to understand and modulate these interactions therapeutically, such that the pathogenic imprinting of proinflammatory memory cells can be extinguished and the anti-inflammatory capacity of the patients' regulatory cells can be restored.

The special program "Osteoimmunology" under the leadership of the Universities of Erlangen, Jena, Gießen and Münster, is investigating in 27 projects clarification approaches on the causes of inflammatory rheumatic diseases, such as rheumatoid arthritis and ankylosing spondylitis with the aim of developing new forms of treatment. The molecular mechanisms involved in bone damage and the interaction between the immune system and bone and cartilage are topics of research.

The host response to Borrelia burgdorferi is likely to play a role in the pathogenesis of Lyme arthritis. Whereas most patients with Lyme arthritis can be cured with antibiotic therapy, approximately 10% of the patients have persistent arthritis for months or even several years after antibiotic treatment. In this study, we tested the hypothesis that the T cell response to one or more antigens of B. burgdorferi is different in patients with treatment-responsive or treatment-resistant Lyme arthritis. For this purpose, 313 B. burgdorferi-specific T cell lines were derived from the synovial fluid or peripheral blood of four patients with treatment-responsive Lyme arthritis and five patients with treatment-resistant arthritis. 87 T cell lines from treatment-responsive Lyme arthritis and 112 lines from the treatment-resistant group were examined for the recognition of five recombinant. B. burgdorferi proteins: outer surface proteins A (OspA), B, C, p39, and p93. In both groups of patients, the T cell lines frequently recognized OspB, and only occasionally recognized OspC, p39, and p93. In contrast, OspA was preferentially recognized by T cell lines from patients with treatment-resistant arthritis, but only rarely recognized by T cell lines from patients with treatment-responsive arthritis (odds ratio 28.4, 95% confidence interval 9.2-87.8, p < 0.005). These results are compatible with the hypothesis that the T cell response to B. burgdorferi OspA is involved in the pathogenesis of treatment-resistant Lyme arthritis.

T helper cells contribute to the induction and maintenance of rheumatic inflammation through the secretion of cytokines. The analysis of Th1 cells expressing interferon-γ, Th17 cells expressing interleukin-17 and the newly described Th1+17 cells could give insight into the pathophysiological mechanisms of rheumatic diseases. This could lead to the development of novel, targeted therapeutic strategies.

The intestinal microbiota contributes to the regulation of the intestinal immune system and protection against intestinal infections. Recent studies revealed that the locally restricted intestinal microbiota affects systemic immunity and influences the induction of autoimmunity.

Biologics and especially therapeutic monoclonal antibodies have an ever increasing impact in the therapy of inflammatory and malignant diseases. They allow a selective blockade of cytokines, receptors and other molecules. This review summarizes the immunological background, the current state and future trends in the development of these therapeutic agents.

T helper (Th) cells are grouped into functionally different subsets (considered hitherto distinct and stable) according to their cytokine production. However, a number of recent findings show a much higher degree of Th cell plasticity and interconvertibility than previously assumed. Therefore, Th effector functions might be subject to therapeutic modulation even in late stages of immunopathological diseases.

In a murine model of T cell-mediated autoimmune disease, experimental autoimmune encephalitis (EAE), 80% of all encephalitogenic T cell clones in H-2u mice use the V beta 8.2 TCR element. To induce EAE in susceptible strains of mice either heat-killed Bordetella pertussis organisms or Bordetella pertussis toxin (PT) must be injected in addition to Ag in CFA. We investigated the mechanisms by which PT facilitates the induction of EAE. Our data show, that PT interferes with the induction of Ag-induced peripheral T cell anergy. Furthermore it has a specific adjuvanticity for the autoantigen pAc1-11 in vivo and acts as a selective mitogen in vitro. We also tested the hypothesis that PT is a bacterial superantigen that specifically expands the V beta 8.2+ subset of T cells, thereby expanding the encephalitogenic T cell clones that are contained in this subset, so that the number of autoreactive T cells is brought over a critical threshold, necessary to induce autoimmune disease. Our data show that PT is not a superantigen. Staphylococcal enterotoxin B, a V beta 8.2-specific superantigen, does not enhance the immune response to the encephalitogenic peptide.

We have used an approach of linking previously characterized T cell epitopes into immunologically complex synthetic peptides in order to investigate the mechanism of immunodominance. Our results show that first, cI12-26 is highly dominant following immunization with the lambda repressor (cI) protein, but is a minor epitope in the context of the cI:NP peptide. In contrast, the dominant epitope in response to the cI:NP peptide is a new junctional epitope, which is composed of sequences derived from both the cI and influenza nucleoprotein (NP) segments of the composite peptide. Second, T cell recognition of cI:NP is not significantly altered by Ag processing, based on results from glutaraldehyde-fixed APC. Third, the relative affinities of cI and cI:NP for MHC binding are similar, based on in vitro competition, excluding competition at the level of MHC binding as the determinant of immunodominance. Taken together, these results are consistent with the hypothesis that immunodominance of cI:NP is determined by peptide conformation, which affects the configuration of peptide binding to MHC, thus altering T cell recognition. In conclusion, immunodominance is not simply a function of the primary amino acid sequence, but is a function of the context of the epitope within the protein molecule.

T-Lymphozyten (T-Zellen) nehmen bei der Bildung von Immunantworten eine wesentliche Rolle ein, da sie einerseits wichtige Effektorzellen des Immunsystems sind und andererseits bedeutende Aufgaben bei der Initiation, der Aufrechterhaltung und der Regulation von Immunantworten erfullen. Wohl am deutlichsten wird die zentrale Rolle dieser Zellpopulation am Beispiel der HIV-Infektion illustriert, in deren Folge es aufgrund eines zunehmenden Mangels an T-Helferzellen zu opportunistischen Infektionen kommt, die letztendlich todlich verlaufen.

Background and objectives Glucose-6-phosphate isomerase (G6PI) immunisation induces acute self-limiting arthritis in DBA/1 mice. Upon depletion of regulatory T cells (Treg s ) it is possible to deliberately switch the outcome towards a chronic, destructive and non-remitting disease. Fibroblast-like synoviocytes (FLS) are important effector cells in rheumatoid arthritis (RA). The objective of this work is to unravel differences at the transcriptomic and miRNomic level between FLS from Treg-depleted mice (chronic) and FLS from not-depleted mice (acute). Materials and methods FLS were isolated from the small joints of G6PI immunised mice either Treg-depleted (chronic) or not-depleted (acute) at day 56 post-immunisation or from healthy mice as a baseline control. A transepitelial resistance assay (MATRIN) was used to test FLS collagen destructive potential, while apoptosis was assessed by serum starvation for 5 days followed by flow cytometry staining. Whole genome expression analysis was realised using mouse 430 2.0 array (Affymetrix). Whole microRNA expression was assessed using TaqMan ® Rodent MicroRNA A Array v2.0 (Applied Biosystems). Results FLS from chronic mice at late stages of arthritis show an increased collagen destructive potential and their sensitivity to apoptosis is reduced. Transcriptomic analysis reveals a strong difference in gene expression between FLS from chronic mice and FLS from acute mice. Stimulation with pro-inflammatory cytokines at different time points modulates gene expression differently in cells from chronic mice, enhancing the expression of genes related to cell adhesion, regulation of apoptosis, cell motion and inflammatory response. Comprehensive miRNA analysis shows a panel of overexpressed and down regulated miRNAs that could have an important role in the regulation of arthritis chronicity. Conclusions FLS from chronic mice are more aggressive and less sensitive to cell death than FLS from acute mice. Whole genome expression analysis confirmed their profound differences at a molecular level. Moreover, stimulation with pro-inflammatory cytokines differentially activates gene expression in FLS from mice with chronic, destructive arthritis. Differences in microRNA expression also confirm these findings. G6PI-induced arthritis mouse model is a useful tool to unravel the role of differentially expressed genes and microRNAs in FLS from chronic mice, in order to discover potential candidates for therapeutic intervention in humans.

Rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are chronic inflammatory diseases that primarily affect the joints. The triggers that activate autoreactive T and B lymphocytes in arthritic patients are still unknown.1 It has been widely assumed, however, that the autoantigens recognised by arthritogenic lymphocytes are joint-specific. This assumption has been challenged by findings from a murine model of …

The mechanisms of IgG anti-double-stranded DNA (anti-dsDNA) antibody induction are incompletely understood. We recently demonstrated a high prevalence of autoantibodies to the C-terminus of SmD1 in patients with systemic lupus erythematosus (SLE) that was closely associated with anti-dsDNA reactivity. The aim of the present study was to analyze the influence of the SmD1 C-terminus on the generation of pathogenic anti-dsDNA antibodies in a murine model of SLE.Female lupus-prone prenephritic (NZB x NZW)F1 mice (NZB/NZW mice) as well as female control BALB/c, NZW, and (BALB/c x NZW)F, mice (CWF1 mice) were subcutaneously injected with keyhole limpet hemocyanin (KLH)-coupled SmD1(83-119). Controls received injections of recombinant SmD1 (rSmD1), KLH-rSmD1, KLH-coupled randomized peptide of SmD1(83-119), ovalbumin, or saline. Animals were monitored for survival and proteinuria and for levels of plasma creatinine, urea, and autoantibodies. In addition, histologic examinations were performed and T cell responses against SmD1(83-119) peptide and rSmD1 protein were determined in SmD1(83-119)-treated and -untreated NZB/NZW mice.Immunization with KLH-SmD1(83-119), but not with control peptide, significantly accelerated the natural course of lupus in NZB/NZW mice, with premature renal failure and increased development of anti-dsDNA antibodies. Control strains of mice remained healthy, with no relevant anti-SmD1(83-119) antibodies detectable even after immunization. In contrast to findings in control mice, a T cell response against SmD1(83-119) was already present in unmanipulated NZB/NZW mice, and this response was further amplified after immunization.The SmD1(83-119) peptide can influence the pathogenic anti-dsDNA response in the NZB/NZW murine lupus model. The data suggest that an SmD1(83-119)-specific T cell response is critical. Therefore, modulation of these autoantigen-specific T cells by tolerance induction may provide a therapeutic approach to specific immunosuppression in lupus.

T helper (Th) cells are grouped into functionally different subsets (considered hitherto distinct and stable) according to their cytokine production. However, a number of recent findings show a much higher degree of Th cell plasticity and interconvertibility than previously assumed. Therefore, Th effector functions might be subject to therapeutic modulation even in late stages of immunopathological diseases.

A prospective study was performed comparing conventional radiography, 3-phase bone scintigraphy, ultrasound, and magnetic resonance imaging (MRI) with precontrast and dynamic postcontrast examinations in 60 patients with various forms of arthritis including rheumatoid arthritis (RA), spondyl-arthropathy, and arthritis associated with connective tissue disease.A total of 840 finger joints were examined clinically and by all 4 imaging methods. Experienced investigators blinded to the clinical findings and diagnoses analyzed all methods independently of each other. The patients were divided into 2 groups. Group 1 included 32 patients (448 finger joints) without radiologic signs of destructive arthritis (Larsen grades 0-1) of the evaluated hand and wrist and group 2 included 28 patients (392 finger joints) with radiographs revealing erosions (Larsen grade 2) of the evaluated hand and/or wrist.Clinical evaluation, scintigraphy, MRI, and ultrasound were each more sensitive than conventional radiography in detecting inflammatory soft tissue lesions as well as destructive joint processes in arthritis patients in group 1. All differences were statistically significant. We found ultrasound to be even more sensitive than MRI in the detection of synovitis. MRI detected erosions in 92 finger joints (20%; 26 patients) in group 1 that had not been detected by conventional radiography.Our data indicate that MRI and ultrasound are valuable diagnostic methods in patients with arthritis who have normal findings on radiologic evaluation.

Reactive arthritis (ReA) and Lyme arthritis together comprise a pair of chronic inflammatory diseases of the joints. Although differing in detail, these relatively rare diseases are related in their immunopathology to the much commoner rheumatoid arthritis (RA), for which they serve as both model and control. The trigger for rheumatoid arthritis is unknown, but for these rarer diseases triggering occurs by certain well-defined bacterial infections. Arthritis is an uncommon outcome of these infections, for reasons unknown, and the development of chronic, as distinct from brief, arthritis is even rarer; again, the reasons are unknown. Not only does knowing the trigger greatly assist us in understanding these diseases, so also does knowing the contrasting pattern of Th1 versus Th2 cytokines observed in RA and ReA. ReA and Lyme arthritis are here considered in the wider setting of infections where chronic morbidity arises first from hypersensitivity, and perhaps finally from autoimmunity, such as occurs in some of the major tropical diseases. The immunology of ReA and Lyme disease is surveyed in detail, concentrating on T cells and including an update on the Lyme vaccine(s). Additional sections deal with the enigma of HLA B27, with epidemiological findings relevant to the chronicity of ReA and to the need for enlarged prospective studies of ReA in the setting of a developing country.

Of 686 hemophiliacs who are being treated at our institution, 402 (59%) are HIV-sero-positive. One hundred seventy-eight heterosexual partners of HIV-infected hemophiliacs have been serologically examined; 19 (11%) are HIV-positive. So far none of the seropositive partners suffers from ARC or AIDS. The rate of heterosexual transmission of HIV is statistically significantly correlated with the CD4+ count of the HIV-infected index patient. No such correlation was found with the index patient's clinical stage or the isolation of HIV from the index patient's blood. Of 39 seronegative female partners who were investigated clinically and immunologically, 17 showed pathologically increased numbers of CD8+ counts. In one case, HIV was transmitted from a female patient with von Willebrand's disease to her husband. As compared to other groups at risk for AIDS, the rate of heterosexual HIV transmission is comparatively low in hemophiliacs. The exact reason for this difference is not yet known. The relevance of the immunopathological findings in seronegative sexual partners of hemophiliacs also remains to be determined.

Am Institut fur Experimentelle Hamatologie der Universitat Bonn werden zur Zeit etwa 780 hamophile Patienten betreut. Serum von 637 dieser Patienten konnte auf das Vorhandensein von Antikorpern gegen HIV (Human Immunodeficiency Virus) untersucht werden. 61% der Untersuchten wiesen Antikorper gegen HIV auf, was auf eine Gesamtzahl von etwa 475 HIV-infizierten Hamophilen schliesen last.

At our institution 686 hemophiliacs are being treated. Of them 402 (59%) are anti-HIV-seropositive. The general use of heat-treated clotting factor products was begun in July 1983, and from May 1984 all patients exclusively used heat-treated clotting factors. Thus, one can assume that infection occurred no later than early 1984 in our patients. Since December 1985 HIV-positive hemophiliacs have regularly been clinically and immunologically examined. Most of the 306 patients who could be investigated were clinically symptom-free at the time of their first visit. However, 45 patients have developed AIDS from 1982 through August 1988. The mean survival time of hemophiliacs with AIDS is less than 6 months. In 36% of those 274 patients who have been followed for a mean period of 14 months the clinical stage of the disease worsened by at least one stage according to the classification system proposed by the Centers for Disease Control. We did not find a correlation between clotting-factor consumption during the years 1984–1986 and the actual clinical stage of the patients. Virus isolation from peripheral blood lymphocytes (PBIs) answered the question whether anti-HIV seropositive hemophiliacs are not only immunized but really infected in many more cases than those revealed by detection of p24 antigen or decline of p24 antibody. Positive viral culture correlated strongly with a drop in CD4+ lymphocytes under the level of 400/µl. However, HIV could not be cultured regularly in advanced cases, suggesting that virus replication in PBLs is not necessarely the cause of depletion of T-helper cells. There is no evidence that the natural history of HIV infection in hemophiliacs is different from that in other HIV-infected patients.

780 hemophiliacs are treated at the Institut fiir experimentelle Hamatologie, University of Bonn. Of these, 61% (475 patients) are infected with HIV.From 1982 through January 1987, 15 of the HIV-infected hemophiliacs developed AIDS. It seems alarming, that 9 patients had theirprimary manifestations of AIDS in 1986 and one in January 1987. The primary manifestations of AIDS were:We describe here the clinical features of the hemophilic AIDS patients and discuss the differences in clinical manifestation and prognosis compared to AIDS-patients belonging to other risk groups.These data are discussed on the background of other clinical, immunological and epidemiological findings in our large cohort of HIV-infected hemophiliacs.

Ende 1985 wurde in Kooperation zwischen der Medizinischen Universitatsklinik Bonn, dem Institut fur Experimentelle Hamatologie und Bluttransfusionswesen der Universitat sowie anderen Instituten und Kliniken des Klinikums Bonn eine gezielte Untersuchung der in diesem Zentrum behandelten 780 Patienten mit Hamophilie gestartet. Ziel dieser Untersuchung ist, den Spontanverlauf der HIV-Infektion bei Hamophilen zu erfassen und mit dem Spontanverlauf in anderen Risikogruppen zu vergleichen sowie prognostisch bedeutungsvolle Parameter zu erarbeiten, die die Prognose eines individuellen Patienten abschatzen lassen. Hierbei steht vor allem die Frage, ob die HIV-Infektion in dieser Risikogruppe anders als bei Angehorigen anderer Risikogruppen verlauft, im Mittelpunkt (s. auch Kamradt et al. 1986 in diesem Band).

395 von 656 am Institut fur experimentelle Hamatologie der Universitat Bonn behandelte Hamophilie-Patienten sind Anti-HIV-positiv. Unterteilt man die Gesamtzahl der hier betreuten Hamophilen in drei Untergruppen, Patienten mit leichter (> 5% Faktor VIII-Restaktivitat), mittelschwerer (1-5% Faktor VIII-Restaktivitat) und schwerer (< 1% Faktor VIII-Restaktivitat) Hamophilie, dann last sich erkennen, das die Patienten mit einer schweren Hamophilie, jene Patienten also, die am meisten Faktor VIII substituiert haben, in weitaus hoherem Mase Anti-HIV-seropositiv sind (375/526 Patienten, 71%) als die Patienten mit einer leichten Hamophilie (6/78 Patienten, 8%). Die Patienten mit einer mittelschweren Hamophilie sind zu 27% (14/52 Patienten) Anti-HIV-positiv. Insgesamt sind 60% aller behandelten Hamophilen Anti-HIV-positiv. Die serologischen Untersuchungsergebnisse sind in Tabelle 1 zusammengefast.

Neurologische Komplikationen bei AIDS kommen in einer Haufigkeit von 23 bis 40% vor (Koppel et al. 1985; Levy et al. 1985). In groseren Autopsieserien wurde aber mit uber 70% ein wesentlich haufigerer Befall des Nervensystems nachgewiesen (Moskowitz et al. 1984). Neurologische Ausfalle konnen sich isoliert oder in Kombination im zentralen oder peripheren Nervensystem manifestieren.