Biomedical subjects

A Hatzakis

Publications and source records attributed to A Hatzakis.

At least 37 records · Page 2Linked to original sources

PubMed2001

T cell receptor excision circles and HIV-1 2-LTR episomal DNA to predict AIDS in patients not receiving effective therapy.

OBJECTIVE: To determine whether improved prediction of AIDS-free survival following HIV-1 seroconversion is achieved by measuring HIV-1 2-LTR episomal DNA (2-LTR) circles and T cell receptor rearrangement excision circles (TREC), reflecting HIV replication and lymphocyte emigration from the thymus, respectively. DESIGN: Subanalysis of a cohort of 154 patients with hemophilia who became HIV positive between 1978 and 1985 and were followed prospectively. METHODS: Relative hazards (RH) of AIDS, in the absence of highly effective anti-HIV therapy, were estimated for age, HIV-1 viral load, CD4 lymphocyte count and levels of HIV-1 2-LTR circles and TREC [per 106 peripheral blood mononuclear cells (PBMC)]. RESULTS: TREC correlated significantly with CD4 cell counts (r = 0.30) and age (r = -0.60). 2-LTR circles correlated significantly with HIV-1 viral load (r = 0.35). If viral load, CD4 lymphocytes and age were included in a proportional hazards model, the risk of AIDS during a median of 11.6 years of follow-up was increased significantly with fewer TREC (adjusted RH, 2.0 per log10 copies/106 PBMC) and more 2-LTR circles (RH, 1.7 per log10 copies/106 PBMC). AIDS prediction with TREC and 2-LTR circles held for most subgroups defined by median viral load, CD4 lymphocytes and age. CONCLUSIONS: PBMC that have high levels of HIV-1 replication and low levels of recent thymic emigrants are associated with a substantially increased risk of AIDS. It is not known if measurement of either TREC or 2-LTR circles will complement HIV-1 viral load as an estimation of the risk of AIDS for patients who are receiving highly effective anti-HIV therapy.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Lack of association of hepatitis C virus load and genotype with risk of end-stage liver disease in patients with human immunodeficiency virus coinfection.

In hepatitis C virus (HCV) infection, virus load and the risk for HCV-related end-stage liver disease (ESLD) are increased among persons with human immunodeficiency virus (HIV) coinfection. To clarify these relationships, 42 hemophilic patients who developed ESLD and random samples from 164 hemophilic patients with HCV infection alone and 146 with HCV-HIV coinfection were tested for HCV load and genotype. HCV genotype was unrelated to HIV and age. In contrast, HCV load was higher with older age (P(trend)=.0001) and with HIV coinfection (6.2 vs. 5.9 log(10) genome equivalents/mL, P=.0001). During 16 years of follow-up of dually infected patients, ESLD risk was unrelated to HCV load overall (P(trend)=.64) or separately to HCV genotype 1 and genotypes 2 or 3 (P(trend)> or =.70). Irrespective of virus load, incidence of ESLD was marginally increased 2-fold (95% confidence interval, 0.8-5.6) with HCV genotype 1. Understanding the discordance between HCV load and ESLD, despite HIV's link to each of these, may help clarify the pathogenesis of HCV-related disease.

Cohort Studies↗

PubMed2001

Prevalence and genotypic distribution of TT virus in Athens, Greece.

The prevalence of TT virus (TTV) infection in various population groups from Athens, Greece, was assessed by the polymerase chain reaction (PCR) using two primer sets from distinct regions of the genome: the conventional set derived from the open reading frame-1 (ORF-1) and the new, highly sensitive set targeting the region that includes the TATA signal localized upstream of ORF-2. Based on both primer sets, TTV DNA was detected in 42/50 (84.0%) healthy individuals, 42/50 (84.0%) chronic hepatitis C patients, 31/39 (79.5%) acute non-A-E hepatitis patients (group I), 14/16 (87.5%) renal failure patients with acute non-A-E hepatitis (group II), 47/50 (94.0%) intravenous drug users (IVDU), 36/50 (72.0%) hemophiliacs, and 21/31 (67.7%) hemodialysis patients. The presence of TTV was not associated with any particular risk group, and no differences were observed in relation to demographic, biochemical and virological characteristics between TTV DNA-positive and -negative patients. TTV did not seem to have a profound effect on the course of chronic C or acute non-A-E hepatitis either. Phylogenetic analysis revealed that TTV strains circulating in the greater metropolitan area of Athens belong not only to the G1 and G2 genotypes that are encountered worldwide, but also to G3 and to G5 that are found mainly in Europe and Asia, respectively. Further studies will shed light on the role of this highly prevalent virus.

Adolescent↗

PubMed2001

Comparative evaluation of the QUANTIPLEX HIV-1 RNA 2.0 and 3.0 (bDNA) assays and the AMPLICOR HIV-1 MONITOR v1.5 test for the quantitation of human immunodeficiency virus type 1 RNA in plasma.

HIV-1 RNA measurements from 84 plasma specimens obtained with the QUANTIPLEX HIV-1 RNA 2.0 and 3.0 (bDNA) assays (Chiron Diagnostics, Emeryville, CA) and with the AMPLICOR HIV-1 MONITOR Test, version 1.5 with ultra-sensitive specimen preparation (Roche Diagnostic Systems, Inc., Branchburg, NJ) were compared. The absolute RNA values of tested specimens differed significantly between bDNA 2.0 and bDNA 3.0 or Monitor v1.5 measurements (Wilcoxon signed-rank test P<0.001). Results generated with bDNA 3.0 or with Monitor v1.5 were approximately twofold greater than those generated with bDNA 2.0, with smaller differences at higher HIV-1 RNA levels and greater differences at RNA levels below 1000 copies per ml. Although highly correlated (r=0.92 and 0.86, respectively), viral load data generated with bDNA 2.0 and either bDNA 3.0 or Monitor v1.5 were in poor agreement. Concordant results (difference in log(10) copies per ml <0.5) were found at frequencies of 80% for bDNA 2.0 and bDNA 3.0 and only at 58.5% for bDNA 2.0 and Monitor v1.5. In contrast, bDNA 3.0 and Monitor v1.5 measurements were highly correlated (r=0.96) and in good agreement (92.7%).

Adult↗

PubMed2001

Prevalence, risk factors and evaluation of a screening strategy for chronic hepatitis C and B virus infections in healthy company employees.

A cross-sectional study was carried out in employees of 17 Greek companies with the aim of assessing the prevalence of hepatitis B (HBV) and hepatitis C (HCV) virus, identifying associated prognostic/risk factors and evaluating the effectiveness of a questionnaire as a pre-screening tool. All participants were asked to complete a questionnaire and a random sample of them was asked to provide a blood sample for hepatitis B core antibody (anti-HBc), hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C (anti-HCV) testing. Individual questions or combinations of them were evaluated in terms of their ability to detect HBV or HCV(+) cases. Of 9085 eligible employees, 6074 (67%) completed the questionnaire. Of 990 samples obtained, 19.9% were anti-HBc(+), 2.6% HBsAg(+) and 0.5% anti-HCV(+). All anti-HCV(+) cases had multiple parenteral risk factors. Multiple logistic regression identified associations between anti-HBc and older age, family members with chronic hepatitis, job category and history of transfusion before 1992. HBsAg(+) was associated with older age and history of transfusion before 1992. None of the risk/prognostic factors had sufficient sensitivity and specificity for HBV but report of at least one risk factor identified all HCV(+) cases. Anti-HCV screening of those with at least two parenteral risk factors not only identified all anti-HCV(+) cases but also resulted in 86% decrease in the screening cost. Under the light of recent treatment advances, targeted questionnaire-based screening of asymptomatic people may prove to be a cost-effective way to face hepatitis C.

Adolescent↗

PubMed2001

Cholestatic syndrome with bile duct damage and loss in renal transplant recipients with HCV infection.

BACKGROUND/AIMS: Bile duct cells are known to be susceptible to hepatitis B and C virus, while it has been recently suggested that hepatitis B virus (HBV) and hepatitis C virus (HCV) infection may have a direct role in the pathogenesis of vanishing bile duct syndrome (VBDS) after liver transplantation. We report the development of a cholestatic syndrome associated with bile duct damage and loss in four HCV-infected renal transplant recipients. METHODS: All four patients were followed up biochemically, serologically and with consecutive liver biopsies. Serum HCV RNA was quantitatively assessed and genotyping was performed. RESULTS: Three patients were anti-HCV negative and one was anti-HCV/HBsAg positive at the time of transplantation and received the combination of methylprednisolone, azathioprine and cyclosporine A. Two patients became anti-HCV positive 1 year and one patient 3 years post-transplantation. Elevation of the cholestatic enzymes appeared simultaneously with seroconversion, or 2-4 years later, and was related to lesions of the small-sized interlobular bile ducts. Early bile duct lesions were characterized by degenerative changes of the epithelium. Late and more severe bile duct damage was associated with bile duct loss. The progression of the cholestatic syndrome coincided with high HCV RNA serum levels, while HCV genotype was 1a and 1b. Two patients (one with HBV co-infection) developed progressive VBDS and died of liver failure 2 and 3 years after biochemical onset. One patient, despite developing VBDS within a 10-month period, showed marked improvement of liver function after cessation of immunosuppression because of graft loss. The fourth patient, who had mild biochemical and histological bile duct changes, almost normalized liver function tests after withdrawal of azathioprine. CONCLUSION: A progressive cholestatic syndrome due to bile duct damage and loss may develop in renal transplant patients with HCV infection. The occurrence of the lesions after the appearance of anti-HCV antibodies and the high HCV RNA levels are indicative of viral involvement in the pathogenesis. Withdrawal of immunosuppressive therapy may have a beneficial effect on the outcome of the disease.

Adult↗

PubMed2001

Low-dose IFN-alpha monotherapy in treatment-naive individuals with HIV-1 infection: evidence of potent suppression of viral replication.

To evaluate the safety and antiviral action of interferon-alpha (IFN-alpha) in HIV-1 infection, we undertook a proof of concept study in 27 treatment-naive patients. Eligible patients comprised two groups: the IFN-alphaT group (n = 17), which received 5 MIU IFN-alpha s.c. daily for 32 consecutive days, and the IFN-alphaNT group (n = 10), which did not receive IFN-alpha prior to highly active antiretroviral therapy (HAART), which was commenced on day 28 in both groups. IFN-alphaTreatment was well tolerated in 14 of the 17 patients of the IFN-alphaT group who completed the study. The mean HIV RNA reduction in the IFN-alphaT group on day 14 was 1.1 log(10). Viral load suppression was inversely associated with baseline viral load (p = 0.031). Four weeks after initiation of HAART, IFN-alphaT and IFN-alphaNT group patients had 2.40 and 1.82 log(10) HIV RNA reduction from baseline, respectively (p < 0.001). There was no evidence of cross-resistance with existing antiretrovirals in patients with HIV-RNA rebound after initial plasma viral load decline > or = 1 log(10) during IFN-alpha monotherapy. Thus, low daily IFN-alpha exhibits potent anti-HIV-1 activity in vivo without serious adverse effects. These properties render IFN-alpha an attractive candidate for further assessment as a constituent of HAART.

Anti-HIV Agents↗

PubMed2001

Molecular characterization of a complex, recombinant human immunodeficiency virus type 1 (HIV-1) isolate (A/G/J/K/?): evidence to support the existence of a novel HIV-1 subtype.

Recombination is one of several factors that contribute to the great genetic diversity of human immunodeficiency virus type 1 (HIV-1). In the current study, analysis of the full-length genome of a novel complex mosaic HIV-1 isolate (99GR303) from a Greek sailor who was possibly infected in Sierra Leone, Africa is presented. The 99GR303 isolate was found to comprise genomic regions belonging to subtypes A, G, J and K as well as of regions of a subtype that remains unclassified. For a partial region of env as well as vpr, no apparent similarity to the known HIV-1 subtypes or to any of the circulating recombinant forms was found. In fact, in the partial env gene, including the C2-V3 region, the 99GR303 isolate formed a new clade, suggesting the existence of an additional HIV-1 subtype. Thus, novel recombinants embody partial genomic regions which may have originated either from subtypes that existed in the past and became extinct or from contemporary subtypes that are extremely rare.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Re-analysis of human immunodeficiency virus type 1 isolates from Cyprus and Greece, initially designated 'subtype I', reveals a unique complex A/G/H/K/? mosaic pattern.

Human immunodeficiency virus type 1 (HIV-1) has been classified into three main groups and 11 distinct subtypes. Moreover, several circulating recombinant forms (CRFs) of HIV-1 have been recently documented to have spread widely causing extensive HIV-1 epidemics. A subtype, initially designated I (CRF04_cpx), was documented in Cyprus and Greece and was found to comprise regions of sequence derived from subtypes A and G as well as regions of unclassified sequence. Re-analysis of the three full-length CRF04_cpx sequences that were available revealed a mosaic genomic organization of unique complexity comprising regions of sequence from at least five distinct subtypes, A, G, H, K and unclassified regions. These strains account for approximately 2% of the total HIV-1-infected population in Greece, thus providing evidence of the great capability of HIV-1 to recombine and produce highly divergent strains which can be spread successfully through different infection routes.

Capsid↗

PubMed2001

Drug therapy in HIV infection--Fifth International Congress.

At present, the optimal clinical management of HIV infection involves therapy with combinations of nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs, respectively) and protease inhibitors (PIs). Although these regimens are effective at reducing mortality and progression to AIDS, they fail to sustain a successful control of HIV RNA levels in a large proportion of patients; at the same time, resistance remains a major clinical problem. Development of novel antiretroviral drugs, with limited or no cross-resistance to existing drugs, that are more potent or that act by different mechanisms, is an obvious strategy to overcome such limitations. This report focuses on clinical trials of such selected drugs that were presented at this congress.

Journal Article↗

PubMed2000

Increased liver decompensation risk with atypical hepatitis C virus antibody levels.

Knowledge of serum markers of liver decompensation would facilitate care of patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. HCV load and anti-c33c and anti-NS5 levels did not distinguish 28 HCV- and HIV-positive predecompensation patients from 28 matched control patients, whereas more patients than controls had high anti-c100(p) and low anti-c22(p). In multivariate analysis, decompensation was associated with high anti-c100(p) titer (>/=1:4050; odds ratio [OR], 3. 4; 95% confidence interval [CI], 1.1-11.5) and low anti-c22(p) (<1:36,450; OR, 3.0; 95% CI, 1.0-10.2) and with antibody band strength at 1:50 dilution (anti-c100[p] OR, 7.0; 95% CI, 1. 7-48.9; anti-c22[p] OR, 7.1; 95% CI, 1.7-49.2). With high anti-c100(p) or low anti-c22(p), sensitivity for decompensation was 86%-96% and specificity was 21%-36%; with both markers, sensitivity was 29%-32% and specificity was 93%-96%. Although the mechanisms for these associations are unknown, if these findings are verified in other populations, anti-c100(p) and anti-c22(p) might be valuable surrogate markers for liver decompensation risk.

Case-Control Studies↗

PubMed2000

Molecular characterization of a recombinant HIV type 1 isolate (A/G/E/?): unidentified regions may be derived from parental subtype E sequences.

Recombination is one of several factors contributing to the genetic diversity of HIV-1, which is divided into group M (itself comprising 11 subtypes, A-K) and two other groups named O and N. In the present study, the full-length genome of an HIV-1 isolate obtained from a Greek subject (GR17) infected in the Democratic Republic of the Congo (formerly Zaire) was analyzed to reveal a novel mosaic sequence composed of subtypes A, G, and E and regions of indeterminate classification. In particular, most of pol and tat/vpu, as well as the region encoding intracellular domain of gp41, did not cluster with any of the previously characterized HIV-1 subtypes. The clustering of the LTR of GR17 with subtype E was suggestive of a subtype E origin of the unclassified regions. However, the identification of distinct characteristics in the LTR, such as two functional NF-kappaB sites and a distinct TAR element, compared with those of circulating (A/E) recombinants, suggests that the partial subtype E sequences found in GR17 and the mosaic viruses (A/E) have not derived from each other. These results provide evidence that parental subtype E may have existed in the geographic area of Central Africa.

Adult↗

PubMed2000

Effect of recent thymic emigrants on progression of HIV-1 disease.

BACKGROUND: The concentration of T-cell receptor-rearrangement excision DNA circles (TREC) in peripheral-blood T cells is a marker of recent thymic emigrant alphabeta T cells. We studied the predictive ability of measurements of TREC for clinical outcome in HIV-1-infected individuals. METHODS: We measured TREC in peripheral-blood mononuclear cells with a real-time PCR assay. We studied 131 Greek participants in the Multicenter Hemophilia Cohort Study who had known HIV-1 seroconversion dates. The prognostic value of baseline TREC, CD4 T-cell count, and HIV-1 RNA concentration was assessed by Kaplan-Meier and Cox's regression analysis. FINDINGS: Four participants had progressed to AIDS by first blood sampling. Among the remaining 127 individuals, the median value of TREC per 10(6) cells was 6900 (IQR 2370-15604). Baseline TREC values were lower in the 53 who progressed to AIDS than in those who did not (geometric mean 2843 [95% CI 1468-5504] vs 6560 [4723-9113] per 10(6) cells; p=0.017). The relative hazard of AIDS, adjusted for plasma viral load, CD4 T-cell count, and age at seroconversion was 1.44 (95% CI 1.04-2.01; p=0.031) per ten-fold increase in TREC; that for death was 1.52 (1.12-2.06; p=0.007). The adjusted relative hazards of death were 2.91 (1.91-4.44; p<0.001) per ten-fold increase in plasma HIV-1 RNA load and 1.20 (1.04-1.38; p=0.014) per 100-cell decrease in CD4 T-cell count. INTERPRETATION: The concentration of TREC in the peripheral T-cell pool complements HIV-1 RNA load and CD4 T-cell count in predicting the rate of HIV-1 disease progression. Recent thymic emigrants have a role in the pathogenesis of HIV-1 disease.

Adult↗

PubMed2000

Molecular epidemiology of GB virus C/hepatitis G virus in Athens, Greece.

The relevance of GB virus C/hepatitis G virus (GBV-C/HGV) infections in liver pathology remains unclear. To investigate the epidemiology of GBV-C/HGV in Athens, Greece, sera from 512 subjects were screened for present and past markers of GBV-C/HGV infection using a reverse transcription-polymerase chain reaction (RT-PCR) and a serological assay, respectively. GBV-C/HGV RNA was detected in 18/56 (32.1%), 12/42 (28.6%), and 16/55 (29.1%) patients with acute hepatitis B, C, or non-A-E, and in 5/58 (8.6%) and 18/68 (26.5%) patients with chronic hepatitis B or C, respectively, as well as in 50/133 (37.6%) hemodialysis patients and 10/100 (10%) healthy individuals. The data indicated that GBV-C/HGV seroprevalence is age-dependent; thus, GBV-C/HGV RNA and anti-E2 positivity were shown to be associated with younger age [odds ratio 0.98, 95% confidence interval (CI) 0. 97-1.00, P = 0.017] and older age (odds ratio 1.03, 95% CI 1.01-1.05, P = 0.002), respectively. No significant associations were identified between GBV-C/HGV RNA status and alanine aminotransferase (ALT) levels in either hepatitis or hemodialysis patients. Nevertheless, GBV-C/HGV RNA-positive acute non-A-E hepatitis patients were more likely to manifest a more severe clinical form of acute hepatitis (P = 0.024). Phylogenetic analysis of partial 5'-untranslated region sequences isolated from 18 viremic individuals showed that most GBV-C/HGV strains circulating in the greater metropolitan area of Athens belong to the 2a subgroup. A genetically diverse type 2 sequence that may represent a novel subtype within group 2 was also characterized.

5' Untranslated Regions↗

PubMed2000

Cholestatic syndromes in renal transplant recipients with HCV infection.

We present two distinct types of cholestatic syndrome identified in eight renal transplant (RTx) patients with HCV infection. Four patients developed fibrosing cholestatic hepatitis (FCH) and four, vanishing bile duct syndrome (VBDS). All patients with FCH were anti-HCV (-) at the time of Tx and developed a cholestatic profile 1-4 months post-Tx, with high HCV-RNA levels. Immunosuppressive therapy was drastically reduced. Two patients died of sepsis and liver failure 16 and 18 months post-Tx, and the other two showed marked improvement and seroconverted to anti-HCV. Regarding the patients with VBDS, three were anti-HCV (-) and one was anti-HCV (+)/HBsAg (+) at the time of RTx. Two patients became anti-HCV (+) 1 year, and one patient, 3 years post-Tx. Two patients developed progressive VBDS and died of liver failure 2 and 3 years after onset, and two showed marked improvement after withdrawal of immunosuppression. In two of the patients, the progression of the disease coincided with elevation in serum HCV RNA levels. We concluded that a progressive cholestatic syndrome acquiring features of FCH or VBDS may develop in HCV-infected RTx patients. The association with high viral load implicated the virus in the pathogenesis. Drastic reduction of immunosuppression may favourably affect the outcome.

Adult↗

PubMed2000

Unusual CD4+CD8+ phenotype in a greek patient diagnosed with adult T-cell leukemia positive for human T-cell leukemia virus type I (HTLV-I).

We describe the first Greek patient diagnosed with Adult T cell leukemia (ATL) characterized by an expansion of CD4+CD8+ double positive lymphocytes. Low levels of plasma antibodies against HTLV-I Env and Gag proteins were detected. Analysis of the the patient's DNA revealed that she was infected by a cosmopolitan strain of HTLV-I. Since HTLV-I usually leads to the expansion of CD4+ cells, this patient illustrates a rare immunophenotype, which suggests that the HTLV-I-induced proliferative response may occur in a pre-T cell stage.

Base Sequence↗

PubMed2000

The AIDS profile in a low risk country: the central role of bisexual men.

BACKGROUND: Policies and measures for the prevention of human immunodeficiency virus Type 1 (HIV-1) transmission require adequate information about the risk profile of AIDS which is time-, place- and population-dependent. We have studied the risk factors for AIDS among men in Greece, a country with relatively low incidence of AIDS. METHODS: A case-control study of all male patients with incident disease, who have been diagnosed in the major university-affiliated, AIDS Unit from February 1995 through August 1997 was conducted in Athens, Greece, a country with relatively low incidence of AIDS. Eighty-three AIDS patients were enrolled and an equal number of orthopaedic patients as controls. All interviews were conducted by the same physician and took place in the hospital. RESULTS: There were no differences among heterosexual men with AIDS, homo- or bi-sexual men with AIDS, and controls with respect to any socio-economic variable. The odds ratio for AIDS among homo- or bi-sexual men, in comparison with heterosexual men, was 51.5 (95% confidence intervals 21.6-122.7). Blood transfusion, intravenous drug abuse and haemophilia were less important risk factors for AIDS in this study. Condom use was generally very low and there was a tendency for lesser use among men at highest risk for HIV transmission, that is, those with a preference for receptive anal intercourse. CONCLUSIONS: AIDS among men in Greece is mainly driven by homosexual behaviour, but the relatively high proportion of bisexual men and the relatively low frequency of condom use are warning signs for the potential of the epidemic to expand in the future. The relatively low incidence of AIDS in Greece, in comparison with other European populations, may be due to a phase difference in the epidemic, but it could also be due to the traditional role separation of homosexuals in this geographical area, and the easy accessibility of disposable syringes and needles in Greece.

Acquired Immunodeficiency Syndrome↗

PubMed1999

The role of immunosuppression and immune-activation in classic Kaposi's sarcoma.

Immunodeficiency and elevated levels of cytokines have been associated with the development of Kaposi's sarcoma (KS) lesions in patients with AIDS and iatrogenic immunodeficiency. However, their role in classic KS (CKS) is unclear. We measured peripheral blood cell levels, including T-cell subsets, as well as neopterin and beta(2)-microglobulin in 91 HIV-negative Greek patients with histologically confirmed CKS and in 107 controls matched for age and sex. CKS cases had slightly lower leukocyte counts (p = 0.08) and lymphocyte counts (p = 0.02). Although the percentage of CD4 and CD8 T-lymphocytes were not significantly different from controls (p = 0.10 and p = 0.45, respectively), CD4 T-lymphocytes were lower in cases than controls (812 cells/microliter and 1,009 cells/microliter, respectively; p = 0.01); part of this difference resulted from the lower lymphocyte counts (p = 0.07 after adjusting for lymphocyte counts). However, neopterin and beta(2)-microglobulin were both considerably elevated [geometric mean (95% CI): 8.35 (7.27-9.73) nmol/L and 2,904 (2,479-3,401) microgram/L in cases and 5.86 (5.40-6. 35) nmol/L and 2,042 (1,880-2,218) microgram/L in controls, respectively]. We conclude that CKS patients are predominantly characterised by immune activation, although an element of minor immunosupression may also be present.

Biomarkers↗