Low levels of the immunoregulator Semaphorin 4D (CD100) in sera of HIV patients.

INTRODUCTION: Semaphorin-4D (CD100), generated by CD4/CD8 T-cells and its receptor on B cells - CD72, play a role in immune regulation. Both have soluble forms - sCD100/sCD72. METHODS: sCD100 and sCD72 levels were determined by ELISA (MyBioSource, USA). RESULTS: 28 chronic HIV patients and 50 matched healthy volunteers participated in our study. Before treatment, CD4 T-cells counts were 267 ±â€¯216 cells/mcl and viral load (VL) was 586,675 ±â€¯1897,431 copies/ml. Two years following HAART, CD4 T-cells counts rose to 475 ±â€¯264 cells/mcl and VL dropped to 2050 ±â€¯10,539 copies/ml. CD8 T-cells counts were stable. sCD72 levels prior (4.13 ±â€¯2.03 ng/ml) and following HAART (3.53 ±â€¯2.01 ng/ml) were similar to control levels (4.51 ±â€¯2.66 ng/ml). sCD100 levels before (40.47 ±â€¯31.4 ng/ml) and following HAART (37.68 ±â€¯29.44 ng/ml) were significantly lower compared to controls (99.67 ±â€¯36.72 ng/ml) despite the significant increase in CD4 T-cells counts. CONCLUSIONS: The permanent low levels of the immunoregulator sCD100 suggest a role for CD100 in the immune dysfunction and T cells exhaustion of HIV.

Auditing HIV Testing Rates across Europe: Results from the HIDES 2 Study.

European guidelines recommend the routine offer of an HIV test in patients with a number of AIDS-defining and non-AIDS conditions believed to share an association with HIV; so called indicator conditions (IC). Adherence with this guidance across Europe is not known. We audited HIV testing behaviour in patients accessing care for a number of ICs. Participating centres reviewed the case notes of either 100 patients or of all consecutive patients in one year, presenting for each of the following ICs: tuberculosis, non-Hodgkins lymphoma, anal and cervical cancer, hepatitis B and C and oesophageal candidiasis. Observed HIV-positive rates were applied by region and IC to estimate the number of HIV diagnoses potentially missed. Outcomes examined were: HIV test rate (% of total patients with IC), HIV test accepted (% of tests performed/% of tests offered) and new HIV diagnosis rate (%). There were 49 audits from 23 centres, representing 7037 patients. The median test rate across audits was 72% (IQR 32-97), lowest in Northern Europe (median 44%, IQR 22-68%) and highest in Eastern Europe (median 99%, IQR 86-100). Uptake of testing was close to 100% in all regions. The median HIV+ rate was 0.9% (IQR 0.0-4.9), with 29 audits (60.4%) having an HIV+ rate >0.1%. After adjustment, there were no differences between regions of Europe in the proportion with >0.1% testing positive (global p = 0.14). A total of 113 patients tested HIV+. Applying the observed rates of testing HIV+ within individual ICs and regions to all persons presenting with an IC suggested that 105 diagnoses were potentially missed. Testing rates in well-established HIV ICs remained low across Europe, despite high prevalence rates, reflecting missed opportunities for earlier HIV diagnosis and care. Significant numbers may have had an opportunity for HIV diagnosis if all persons included in IC audits had been tested.

Syphilis and HIV co-infection in an Israeli HIV clinic: incidence and outcome.

The re-emergence of syphilis among HIV-infected patients has been reported in recent years. We evaluated co-infection among heterosexual immigrants in an Israeli AIDS center. The records of 1060 HIV-infected patients were evaluated for positive syphilis serology between the years 2000 and 2005, and all seropositive patients were further evaluated. We found 150 HIV/syphilis co-infected patients (57% men, 93% of African origin), of who 135 were found to have late latent syphilis. Lumbar puncture (LP) was performed in 51 patients, 16 (31%) had abnormal cerebrospinal fluid (CSF) compatible with neurosyphilis. Abnormal CSF correlated with the absence of previous anti-syphilis treatment, but not with CD4 count, viral load or Venereal Disease Research Laboratory titres. Penicillin was recommended to all patients according to their disease stages and 81 patients completed 12 months post-treatment follow-up. Twenty-one of 81 (26%) treatments were successful, 33 (41%) showed 'serofast reaction' and 27 (33%) failed therapy. In conclusion, a high incidence of syphilis with CSF reactivity suggestive of neurosyphilis was observed in heterosexual Ethiopian HIV-infected patients. Thus, repeated serological screening and CSF evaluation seems to be indicated in these patients. Penicillin therapy resulted in 'serofast reaction' or treatment failure for most patients. More, intensive treatment might be needed for HIV/syphilis in co-infected patients, especially those with severe immune-deficiency and prolonged syphilis infection.

Prevention of human immunodeficiency virus mother-to-child transmission in Israel.

The objective of the study was to investigate the HIV-mother-to-child transmission (MTCT) rate in Israel. This was a retrospective study of HIV-infected pregnant women, mainly immigrants from Ethiopia, in six Israeli AIDS centres, in 2000-2005. Medical records of mothers and newborns were evaluated for HIV status, treatment and MTCT rates. Three hundred pregnancies of 241 HIV-infected women, resulting in 304 live births, were studied. In 86/241(36%) women, HIV diagnosis was made during the current pregnancy or shortly after labour. Thirty others were diagnosed during previous pregnancies. Highly active antiretroviral therapy (HAART) was prescribed in 76% of pregnancies. The mean viral load before labour was 23,000 +/- 100,000 copies/mL with a mean CD4 of 406 +/- 223 (range 4-1277) cells/mm(3). Caesarian sections were preformed in 175/300 pregnancies (103/175 with viral load <1000 copies/mL). During labour, azidothymidine (AZT) was given to 80% and nevirapine to 8% of the women. Eighty-eight percent of the neonates received AZT for six weeks. The overall HIV-MTCT rate was 3.6%. MTCT correlated significantly with delayed HIV diagnosis, low CD4, lack of HAART during pregnancy and lack of perinatal treatment. HIV treatment of mothers and their newborns throughout pregnancy, labour and perinatal period are crucial for effective prevention of MTCT, emphasizing the need for early HIV screening, diagnosis and treatment.

Interleukin-18 binding protein in the sera of patients with Wegener's granulomatosis.

INTRODUCTION: In the present study, we examined the levels of the pro-inflammatory cytokine IL-18 and its natural inhibitor, the IL-18 binding protein (IL-18BP), in sera of Wegener's granulomatosis (WG) patients at various stages of the disease. PATIENTS AND METHODS: Sera from eight consecutive biopsy-proven systemic WG patients (four men and four women; age at diagnosis 58.4 +/- 13.8 years) were obtained longitudinally with a follow-up period of 55.2 +/- 30 months. Sera obtained from 50 healthy subjects were used as controls. RESULTS AND DISCUSSION: Serum levels of IL-18, IL-18BP, and free IL-18 obtained during an active phase of the disease (Birmingham Vasculitis Activity Score, BVAS > 10) were more than twofold higher than levels in the same patients during inactive disease stages (BVAS < 5; P < 0.002; P < 0.006, and P < 0.03 for IL-18, IL-18BP, and free IL-18, respectively). During inactive stages, the levels of these markers were comparable to those of healthy controls. The elevated levels of IL-18 and IL-18BP in sera during active stages of disease suggest a possible role in the pathogenesis and course of the WG. CONCLUSION: Despite the elevated IL-18BP levels during active disease, free IL-18 remained higher than in the inactive disease stages, suggesting a potential benefit of administration of exogenous IL-18BP as a novel therapeutic approach for active WG.

Internal jugular vein thrombosis following mild ovarian hyperstimulation syndrome in women with factor V Leiden mutation.

OBJECTIVE: To study two women who presented with internal jugular vein thrombosis that developed shortly after in vitro fertilization (IVF) therapy complicated by mild ovarian hyperstimulation syndrome (OHSS). METHODS: Evaluation of the past medical history, treatment, laboratory studies, and clinical outcome of both patients. RESULTS: The two patients were found to be carriers for factor V Leiden mutation (FVLM). One was homozygote and the other heterozygote for that mutation. The genetic predisposition probably contributed to the development of an early thrombosis in these patients despite the mildness of their OHSS. In the homozygote patient, the dose of low molecular weight heparin was reduced due to vaginal bleeding. Afterwards, fetal loss due to an extensive placental infarction occurred. Infarction was confined to maternal side while the fetal side vessels were spared. CONCLUSION: We suggest that women of European descent, especially those with personal or familial history of thromboembolic events, should be screened for FVLM before IVF treatment. In those found to be carriers of FVLM, preventive anticoagulation should be considered.

Dermatomyositis following the diagnosis of ovarian cancer.

We present a case history of a woman who developed dermatomyositis following the diagnosis of stage IV ovarian cancer. Dermatomyositis is a rare paraneoplastic syndrome that usually precedes the diagnosis of ovarian cancer by several months or years. Ours is the fifth reported case of dermatomyositis after an established diagnosis of ovarian cancer in the literature.

Autoantibodies to a NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of autoantibodies directed against an epitope of the glutamate/N-methyl-D-aspartic acid (NMDA) receptor subunit NR2A (which is highly expressed in human brain) in the sera of lupus patients, and to investigate the possible correlation of these antibodies with clinical and serological manifestations of systemic lupus erythematosus (SLE). METHODS: Sera were obtained from 109 consecutive SLE patients. Controls were 65 patients with myasthenia gravis, 19 with autoimmune polyendocrine syndrome type I (APS I), and 65 healthy donors. A 15 amino acid long peptide based on a sequence within the NR2A subunit of the NMDA/glutamate receptor was synthesised. Antibodies to this peptide were determined by enzyme linked immunosorbent assay. Antibodies against double stranded DNA (dsDNA) were measured by Chrithidia luciliae assay. Disease activity was determined using the SLE disease activity index (SLEDAI). RESULTS: Sera of 34/109 SLE patients (31%) reacted specifically with the NR2A peptide compared with only 4/65 myasthenia gravis patients (6.1%, p<0.001), 1/19 APS I patients (5.3%, p<0.02), and 3/65 healthy controls (4.6%, p<0.001). No correlation was found between the presence of NR2A and dsDNA or anti-cardiolipin specific autoantibodies. In addition, no significant correlation was observed between the presence of NR2A specific antibodies and the SLEDAI score or any lupus related clinical manifestations. CONCLUSIONS: A significant number of SLE patients (31%) have NR2A specific antibodies that do not correlate with anti-dsDNA antibodies. Additional studies of lupus patients with neurological disorders should elucidate the role of NR2A specific antibodies in lupus related CNS manifestations.

Drug-resistant HIV infection among drug-naive patients in Israel.

BACKGROUND: In Israel, <0.06% of the general population is infected with human immunodeficiency virus (HIV), with a much higher prevalence among specific groups. These groups are distinguished demographically by risk behavior category and by virus subtype. We investigated transmission of drug resistance within groups to assess the impact of these factors. METHODS: Plasma samples from >15% of all patients with new diagnoses of HIV infection were randomly collected between June 1999 and June 2003. Sequences from 176 drug-naive patients included 20 of subtype A, 20 of subtype AE, 2 of subtype AC, 29 of subtype B, 100 of subtype C, and 5 of subtype F. RESULTS: Major drug resistance mutations (protease: L90M; reverse transcriptase: M41L, K103N, V106M, M184V, Y181S, G190A, L210W, T215Y/F, and K219R) were detected in 1 subject with A subtype, 3 with subtype B, and 9 with subtype C. In addition, 1 subject with A subtypes, 2 with subtype B, and 10 with subtype C had secondary mutations (protease: M46I; reverse transcriptase: A98G, K101Q, and V108I). Only 1 patient had mutations associated with >1 class of drugs. Among subjects who contracted HIV infection in Israel, 16 of 56 (1 of 7 with subtypes A or AE, 4 of 17 with subtype B, and 11 of 32 with subtype C; P=.7-1.0) carried resistant virus--a significantly higher proportion (P<.001) than in subjects infected in other countries (10 of 120 infected). CONCLUSIONS: Drug-resistant virus was detected in 14.8% of patients with new diagnoses of HIV infection but in 28.6% of patients known to have been infected in Israel. The implications include a need for pretreatment resistance testing and for better programs aimed at prevention of transmission, directed particularly at patients. We did not find significant differences in transmission of resistant virus between those infected with subtypes B and C, despite the different demographic background. A conclusive analysis and interpretation should await a more extensive study.

Amelioration of lupus manifestations by a peptide based on the complementarity determining region 1 of an autoantibody in severe combined immunodeficient (SCID) mice engrafted with peripheral blood lymphocytes of systemic lupus erythematosus (SLE) patients.

A peptide based on the complementarity determining region (CDR)1 of a human monoclonal anti-DNA autoantibody (hCDR1) was shown to either prevent or treat an already established murine lupus in systemic lupus erythematosus (SLE)-prone mice or in mice with induced experimental SLE. The present study was undertaken to determine the therapeutic potential of hCDR1 in a model of lupus in severe combined immunodeficient (SCID) mice engrafted with peripheral blood lymphocytes (PBL) of patients with SLE. To this end, PBL obtained from lupus patients were injected intraperitoneally into two equal groups of SCID mice that were treated either with the hCDR1 (50 micro g/mouse) once a week for 8 weeks, or with a control peptide. Mice were tested for human IgG levels, anti-dsDNA autoantibodies, anti-tetanus toxoid antibodies and proteinuria. At sacrifice, the kidneys of the successfully engrafted mice were assessed for human IgG and murine complement C3 deposits. Of the 58 mice transplanted with PBL of SLE patients, 38 (66%) were engrafted successfully. The mice that were treated with the control peptide developed human dsDNA-specific antibodies. Treatment with hCDR1 down-regulated the latter significantly. No significant effect of the treatment on the levels of anti-tetanus toxoid antibodies could be observed. Treatment with hCDR1 resulted in a significant amelioration of the clinical features manifested by proteinuria, human IgG complex deposits as well as deposits of murine complement C3. Thus, the hCDR1 peptide is a potential candidate for a novel specific treatment of SLE patients.

Beneficial effects of the anti-oestrogen tamoxifen on systemic lupus erythematosus of (NZBxNZW)F1 female mice are associated with specific reduction of IgG3 autoantibodies.

BACKGROUND: Sex hormones have been shown to influence the immune system and to modify the course of autoimmune disorders. OBJECTIVE: To examine the effects of the oestrogen antagonist tamoxifen on the course of systemic lupus erythematosus (SLE) in (NZBxNZW)F1 mice. METHODS: Groups of 8 week old (NZBxNZW)F1 female mice were treated with tamoxifen (800 micro g/mouse; twice a week) or with double distilled water for four months. Mice were evaluated monthly for the presence of autoantibodies directed against DNA and nuclear extract (NE) by enzyme linked immunosorbent assay (ELISA). White blood cells and thrombocytes were quantified by a cell counter and proteinuria by combistix kit. At 6 months of age, all mice that did not die spontaneously were killed and evaluated for the presence of glomerular immune deposits by indirect immunofluorescence assay. IgG isotypes of autoantibodies in the mouse sera and glomeruli were determined by gamma chain specific antibodies. RESULTS: Tamoxifen treatment significantly reduced autoantibody production directed against either NE or DNA. The latter reduction was mainly in autoantibodies of the IgG3 isotype. Furthermore, tamoxifen had significant beneficial effects on the course of SLE in (NZBxNZW)F1 mice. At 6 months of age, 40% of the untreated mice died spontaneously, whereas all the tamoxifen treated mice were still alive. All untreated mice showed severe thrombocytopenia and persistent proteinuria, with diffuse glomerular immune deposits of IgG2a and IgG3 isotypes in their kidneys. In contrast, the tamoxifen treated mice had a normal number of thrombocytes and only minimal proteinuria. Moreover, glomerular immune deposits were detected in <40% of the tamoxifen treated mice. The latter were mainly of the IgG2a but not of the IgG3 isotype. CONCLUSION: The results clearly show the remarkable therapeutic effects of tamoxifen on SLE of (NZBxNZW)F1 female mice and suggest that these beneficial effects are related to the specific reduction of IgG3 autoantibodies.

Modulation of autoreactive responses of peripheral blood lymphocytes of patients with systemic lupus erythematosus by peptides based on human and murine anti-DNA autoantibodies.

Two peptides, based on the sequences of the complementarity-determining regions (CDR) 1 and 3 of a pathogenic murine monoclonal anti-DNA autoatibody that bears the 16/6 idiotype (Id), were shown to either prevent or treat an already established systemic lupus erythematosus (SLE) in two murine models of lupus. Two additional peptides based on the human monoclonal anti-DNA, 16/6 Id were synthesized. This study was undertaken in order to investigate the ability of the CDR-based peptides to immunomodulate SLE-associated responses of peripheral blood lymphocytes (PBL) of SLE patients. PBL of 24 of the 62 SLE patients tested proliferated in vitro following stimulation with the human 16/6 Id. Peptides based on the CDRs of both the human and murine anti-DNA autoantibodies inhibited efficiently and specifically the 16/6 Id-induced proliferation and IL-2 production. The latter inhibitions correlated with an up-regulated production (by 2.5-3.5-fold) of the immunosuppressive cytokine, TGF-beta. Overall, the results of our study demonstrate that the CDR-based peptides are capable of down-regulating in vitro autoreactive T cell responses of PBL of SLE patients. Thus, these peptides are potential candidates for a novel specific treatment of SLE patients.

Activity of matrix metalloproteinase-9 is elevated in sera of patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the increased production of autoantibodies and by systemic clinical manifestations and damage to multiple organs. The aim of the present study was to analyse matrix metalloproteinase (MMP)-9 activity in sera of patients with active and inactive SLE in order to evaluate its role in the pathogenesis and course of the disease, as well as its diagnostic value. We measured activity levels of MMP-9 and MMP-2, using both gel zymography and activity assay kits, in sera of 40 SLE patients and of 25 healthy controls. We found that MMP-9 activity, but not MMP-2 activity, is significantly elevated in the sera of SLE patients compared with sera samples of healthy controls. High activity levels of MMP-9 were determined in sera of 68% of the SLE patients. Elevated levels of MMP-9 were correlated with the presence of discoid rash, Raynaud phenomenon, pneumonitis, mucosal ulcers and anti-phospholipid antibodies. Changes in activity levels of MMP-9, but not of MMP-2, were observed in sera of the same patient at different periods of the disease course. High levels of MMP-9 did not correlate with disease activity index (SLEDAI, BILAG) in female patients, but correlated with SLE activity in the group of male patients. The results of the present study suggest that MMP-9 plays a role in the pathogenesis of SLE.

Limited polyarteritis nodosa of the male and female reproductive systems: diagnostic and therapeutic approach.

BACKGROUND: Polyarteritis nodosa (PAN) is a multisystem necrotising small and medium sized vasculitis that when left untreated carries a grave prognosis, with a five year survival of 10-15%. Prolonged immunosuppressive treatment with cyclophosphamide and steroids leads to high remission rates while carrying the risk of life threatening complications. The diagnostic and therapeutic approach for patients with isolated genital tract PAN is not well defined. OBJECTIVE: To present the management and follow up of two patients with limited PAN localised to the male and female reproductive system. CASE REPORTS: A 26 year old man presented with an "acute scrotum". He was afebrile and had no other sign or symptom. Laboratory tests, including complete blood count, erythrocyte sedimentation rate, liver and renal function tests, C reactive protein, antinuclear antibody, cryoglobulins, complement levels, antineutrophil cytoplasmic antibodies, and hepatitis B surface antigen, were all normal. His left testis was excised. Histopathology disclosed PAN of medium sized arteries with testicular infarction but no signs of torsion or infection. The other patient was a 51 year old woman who had had a total hysterectomy for a uterine myoma; incidentally PAN of the uterus and fallopian tubes was discovered. Neither patient received any immunosuppressive treatment after surgical removal of the affected organ. On prolonged follow up (clinical and laboratory evaluation) both patients are healthy with no sign of local recurrence or systemic PAN.

A novel IL-18BP ELISA shows elevated serum IL-18BP in sepsis and extensive decrease of free IL-18.

IL-18 binding protein (IL-18BP) is a circulating antagonist of the proinflammatory Th1 cytokine IL-18. It effectively blocks IL-18 by forming a 1:1 high affinity (Kd=400 pM) complex, exhibiting a very low dissociation rate. We have developed a sandwich ELISA for IL-18BPa and determined its limit of detection (62 pg/ml). Interference by IL-18 and related cytokines, as well as cross reactivity with other IL-18BP isoforms (b, c, and d) were determined. Using this ELISA, we measured serum IL-18BPa in large cohorts of healthy individuals and in septic patients. Serum IL-18BPa in healthy individuals was 2.15+/-0.15 ng/ml (range 0.5-7 ng/ml). In sepsis, the level rose to 21.9+/-1.44 ng/ml (range 4-132 ng/ml). Total IL-18 was measured in the same sera by an electrochemiluminescence assay and free IL-18 was calculated based on the mass action law. Total IL-18 was low in healthy individuals (64+/-17 pg/ml) and most of it ( approximately 85%) was in its free form. Total IL-18 and IL-18BPa were both elevated in sepsis patients upon admission (1.5+/-0.4 ng/ml and 28.6+/-4.5 ng/ml, respectively). At these levels, most of the IL-18 is bound to IL-18BPa, however the remaining free IL-18 is still higher than in healthy individuals. We conclude that IL-18BPa considerably inhibits circulating IL-18 in sepsis. Yet, exogenous administration of IL-18BPa may further reduce circulating IL-18 activity.

[Gastrointestinal hemorrhage of obscure origin].

Gastrointestinal bleeding of obscure origin consists of recurrent bouts of acute or chronic bleeding for which no definite source is discovered in routine endoscopic and barium contrast studies of the upper and lower gastrointestinal tracts. Usually its cause is angiodysplasia of the intestine, but many cases are due to tumors, mostly of the small bowel, which may be malignant. In patients under the age of 50, the proportion with malignancy is relatively high (up to 14%) as compared to older patients. We describe a 45-year-old woman who suffered from gastrointestinal bleeding for 3 years. The cause of bleeding was not found despite extensive work-up. In her last admission for acute gastrointestinal hemorrhage she was given a total of 30 units of blood. A tumor of the small intestine found by angiography was excised and found to be a stromal tumor of uncertain malignant potential. 1 year after operation she is asymptomatic without bleeding and her hemoglobin is stable without treatment.

Immune response of SLE patients to peptides based on the complementarity determining regions of a pathogenic anti-DNA monoclonal antibody.

We have examined the humoral and cellular responses of SLE patients to peptides based on the complementarity-determining regions (CDR) of a monoclonal anti-DNA antibody with a major idiotype- 16/6 Id, in comparison to their responses to the whole 16/6 Id-bearing antibody. Sera of 63% of the SLE patients had antibodies that bound the 16/6 Id, 80% had antibodies to one of the CDR-based peptides, and 40% of the patients reacted with both CDRs. Sera of only a few controls reacted with either the 16/6 Id (6%) or the CDR based peptides (4%) (P < 0.01). Peripheral blood lymphocytes (PBL) of 39% of the patients proliferated in response to the 16/6 Id or to one of the CDR-based peptides (37%), while in the control group the proliferation rates were 66% to the 16/6 Id and 59% to one of the CDR-based peptides (P < 0.05). The correlation between (both) the humoral and cellular immune responses to the CDR-based peptides and to the 16/6 Id suggests the relevance of these peptides to the 16/6 Id and provides additional information on the pathogenic moiety of the latter antibody.

Anticardiolipin autoantibodies in serum samples and cryoglobulins of patients with chronic hepatitis C infection.

OBJECTIVE: Chronic hepatitis C virus (HCV) has been linked to extrahepatic autoimmune phenomena. In addition, a variety of autoantibodies are found in patients with HCV. The prevalence, nature, and clinical significance of anticardiolipin (aCL) autoantibodies in serum samples of patients with HCV were therefore investigated. PATIENTS AND METHODS: A prospective study of 48 consecutive patients with chronic HCV with no evidence of previous hepatitis B virus (HBV) infection or any other autoimmune disorder. Thirty patients with HBV and 50 healthy volunteers matched for age and sex served as control groups. Anticardiolipin antibodies in the serum samples and cryoprecipitates were measured by a sensitive enzyme linked immunosorbent assay (ELISA). The beta(2) glycoprotein I (beta(2)-GPI) dependency was determined by carrying out aCL assays in the presence or absence of fetal calf serum samples. RESULTS: High levels of IgG aCL antibodies were detected in serum samples of 21/48 (44%) patients with HCV. These autoantibodies showed no beta(2)-GPI dependency. The control groups had much lower levels of aCL antibodies (20% in the patients with HBV and none in the normal volunteers). Cryoprecipitates from four patients with HCV (three aCL positive; one aCL negative) were further isolated. In two of the three aCL positive patients, specific cardiolipin reactivity was shown in the cryoprecipitates. The group of patients with HCV and aCL antibodies in their serum showed significantly higher total IgG levels, a higher incidence of antinuclear antibodies, and viraemia (HCV RNA) than the aCL negative patients. None of the patients with HCV and aCL antibodies showed any clinical manifestations related to those autoantibodies. CONCLUSIONS: This study clearly shows a high prevalence of IgG aCL antibodies in the serum of patients with HCV and the localisation of these antibodies in some cryoprecipitates. The role of these autoantibodies on the course of HCV infection and their clinical significance has not yet been determined.