Elevated neopterin and beta 2-microglobulin levels in blood and cerebrospinal fluid occur early in HIV-1 infection

Neopterin and beta 2-microglobulin (beta 2-M) concentrations in cerebrospinal fluid (CSF) and blood were measured in 56 individuals in various stages of HIV-1 infection. Elevated levels of neopterin as well as beta 2-M were found in the CSF of three patients with primary HIV-1 infection and also in subjects in the early stages of chronic HIV-1 infection, with the highest levels in HIV-1 isolation-positive people. There was a clear correlation between the concentrations of the two substances and the levels seemed to increase in parallel with progress of infection. A similar pattern was found in blood. Higher concentrations of neopterin and beta 2-M in CSF than in blood were found in patients with advanced dementia in particular. These findings indicate that the cellular immune system in the central nervous system (CNS) may be activated during the early stages of HIV-1 infection without concomitant overt neurological symptoms. The pathological processes in CNS and blood seem to develop in parallel rather than being restricted to one compartment.     

Continuing intrathecal immunoactivation despite two years of effective antiretroviral therapy against HIV-1 infection

OBJECTIVE: To study the effect of antiretroviral combination treatment on intrathecal immunoactivation in HIV-1 infection. METHOD: Lumbar punctures were performed at baseline, and after 4 months, 1 and 2 years on 30 neurologically asymptomatic, treatment-naive HIV-1-infected patients started on antiretroviral treatment with three or more drugs. Levels of neopterin, beta2-microglobulin and HIV-1 RNA were measured in cerebrospinal fluid (CSF) and blood. RESULTS: All patients continued the study until the 4-month follow-up, although seven discontinued before the 1-year control, and an additional five discontinued before the control after 2 years. Neopterin, beta2-microglobulin and HIV-1 RNA decreased significantly both in CSF and blood, but although 100% of the patients decreased their CSF concentrations of beta2-microglobulin and HIV-1 RNA to normal levels, only 55% had normal CSF neopterin concentrations after 2 years treatment. CONCLUSIONS: In addition to CSF viral load, antiretroviral combination therapy substantially decreases the intrathecal immunoactivation as reflected by CSF neopterin and beta2-microglobulin in neuroasymptomatic HIV-1-infected patients. However, almost half of the patients still have slightly increased CSF neopterin concentrations after 2 years of effective treatment, which might reflect an ongoing low-grade viral replication in brain tissue.     

Cerebrospinal fluid viral load, virus isolation, and intrathecal immunoactivation in HIV type 2 infection

Four patients with HIV-2 infection were followed longitudinally with cerebrospinal fluid (CSF) analyses. Two patients had positive CSF HIV-2 isolations. These two patients had CD4 cell count below 200 x 10(6)/liter and maximum CSF HIV-2 RNA viral loads above 4000 copies/ml. Intrathecal immune activation was demonstrated by elevated CSF neopterin concentrations (14-18 nmol/liter). No opportunistic infections were diagnosed. After antiretroviral treatment CSF viral counts decreased to below 125 copies/ml and CSF neopterin concentrations decreased. In two other patients who had CD4 counts within the normal range CSF virus isolations were repeatedly negative and viral CSF loads were below 125 copies/ml. However, a slightly elevated CSF neopterin concentration in one sample and pleocytosis in another might also be caused by HIV-2 in these patients. Before antiretroviral treatment HIV-2 isolations from blood were positive in all four patients. Maximum HIV-2 RNA viral loads were higher in blood than in CSF. Treatment failure in one patient with increasing viral loads in blood did not result in viral rebound in CSF.     

Urinary neopterin levels in acute viral hepatitis

Elevated neopterin levels in blood or urine have been shown to be a marker for the activation of cell-mediated immunity in vitro and in vivo. To evaluate whether neopterin levels are elevated in patients with acute viral hepatitis, we measured urinary levels in 13 patients with hepatitis A, 26 with hepatitis B, 12 with non-A, non-B hepatitis, 8 with jaundice and/or cholestasis due to biliary and pancreatic disorders and 3 with alcoholic hepatitis and in 62 apparently healthy HBsAg carriers. Neopterin levels in patients with virus-induced hepatitis were significantly higher than those in patients with other diagnoses. Urinary neopterin levels were above normal in 49 of 51 patients with viral hepatitis and elevations during the course of hepatitis showed a pattern similar to that of the usual liver biochemical tests, suggesting that neopterin levels were related to the clinical activity of the viral disease. In patients with nonviral biliary and hepatic disorders, neopterin levels were usually normal and did not correlate with other liver biochemical tests. These findings suggest that cell-mediated immune mechanisms are activated during viral hepatitis and that neopterin measurement may be of value as an additional surrogate marker for non-A, non-B hepatitis.     

Cerebrospinal fluid and serum neopterin and biopterin in D-retrovirus-infected rhesus macaques (Macaca mulatta): relationship to clinical and viral status

Increases in serum and cerebrospinal fluid (CSF) neopterin concentrations accompany many inflammatory diseases, including infection with HIV-1 and may reflect activation of guanosine triphosphate (GTP) cyclohydrolase 1 by gamma-interferon and other cytokines. In the present study, macaques with clinical simian AIDS (SAIDS) infected with the immunosuppressive type-D retrovirus D/1/California had increased concentrations of CSF neopterin but not of biopterin beginning soon after seroconversion. Normal neopterin concentrations in the CSF were found in macaques with SAIDS-related complex as well as asymptomatic, viremic macaques. CSF biopterin, serum neopterin and serum biopterin concentrations of D/1/California-infected macaques were not different from the levels in control animals. The increase in CSF neopterin may reflect local inflammatory responses and paralleled previously documented changes in L-tryptophan metabolism in these macaques. However, the absence of macrophage infiltrates in the brain of the infected macaques suggests a non-macrophage source of both increased CSF neopterin and tryptophan metabolites in the SAIDS macaques.     

Serum neopterin levels in patients with non-alcoholic steatohepatitis

Aim:  Neopterin is a marker of cell-mediated immunity. It also has a fundamental role in host-defense reactions, including interactions with reactive oxygen intermediates and the promotion of local and systemic oxidative stress. The present study aimed to assess the importance of serum neopterin levels in patients with non-alcoholic steatohepatitis (NASH).
Methods:  Thirty-nine patients with NASH diagnosed by liver biopsy and 32 healthy adults (controls) were enrolled in the study. Serum neopterin levels were measured with an enzyme-linked immunosorbent assay in addition to other biochemical parameters, including liver enzymes. Histopathological examinations were graded as suggested by both the necroinflammatory activity grading system and the NASH scoring system.
Results:  The mean serum neopterin levels were higher in patients with NASH compared to the controls (24.1 ± 16.4 vs 16.2 ± 9.5, P  = 0.019). The histological examination of liver biopsies revealed that 34 of the patients with NASH had grade 1 steatohepatitis and only five patients had grade 2 steatohepatitis. A higher serum mean neopterin level was detected in grade 2 patients compared to grade 1 (40.6 ± 5.6 vs 21.7 ± 16.1, P  = 0.014). A gradual increase was also observed in serum neopterin levels with the increase of the NASH score.
Conclusion:  The serum neopterin levels were significantly higher in patients with NASH compared to the controls, and levels showed an association with the severity of liver damage.     

Correlation between neopterin,interferon-gamma and haemoglobin in patients with haematological disorders

Abstract: In this study, we further investigated a possible link between activation of cell-mediated immunity and anaemia in patients with haematological neoplasias. We compared serum concentrations of interferon-gamma and neopterin with haemoglobin levels. Significantly increased interferon-gamma and neopterin concentrations indicated persistent activation of cell-mediated immunity. Neopterin levels correlated significantly to interferon-gamma concentrations and inversely to haemoglobin levels. The data indicate an association between activated macrophages and the development of anaemia in patients with haematological neoplasias.     

Evaluation on HIV serology and immune-stimulation on patients in Tanzania

Antibodies against human immunodeficiency virus, other infectious agents and neopterin levels were determined in 253 patients in a rural area of North-West Tanzania. Seroprevalence for HIV was 3.2%. In one case serology was positive for HIV-1 and HIV-2 antibodies and questions whether there was a real double infection or a cross reaction not only concerning core region proteins but also transmembrane protein. The specificity in the diagnosis of HIV-infection is markedly increased with newer serological methods using recombinant peptides but did not improve sensitivity on African sera. Neopterin was determined as a sensitive indirect marker for the activation of T-cells and is therefore correlated with the susceptibility of HIV infection and with progression of disease. High seroprevalence rates for various infectious agents were determined and may explain the high rate of elevated neopterin levels in 80% of the Africans. Neopterin levels were even higher in HIV patients. Viral p24 antigen was found only in two persons, one of whom had no antibodies detectable.     

Neopterin, β2-Microglobulin,and Acute Phase Proteins in HIV-1-Seropositive and -Seronegative Zambian Patients with Tuberculosis

Neopterin is a biochemical marker for the activation of the cell-mediated immune system. We measured neopterin, β₂-microglobulin, and acute phase proteins in 31 HIV-seropositive and -seronegative Zambian patients with tuberculosis, using stored sera that had been obtained at the beginning and at end of antituberculosis treatment. In both HIV-seropositive and -seronegative patients neopterin and acute phase proteins were elevated when tuberculosis was initially diagnosed and fell during treatment. In contrast, the mean β₂-microglobulin level increased during antituberculous therapy in the HIV-seropositive group. Serum neopterin levels at diagnosis were correlated with other parameters of disease activity (fever, anemia, and weight loss). In both groups, patients with persistently elevated neopterin levels at the end of treatment were more likely to suffer relapse of tuberculosis or other adverse health events in the subsequent follow-up period. Neopterin can be used to monitor the response to antituberculous therapy in both HIV-seropositive and -seronegative patients and may have a prognostic value for the patients' wellbeing in the follow-up period. Accepted for publication: 13 December 1996     

HIV-1-specific antibodies in cerebrospinal fluid mediate cellular cytotoxicity and neutralization

Antibodies mediating HIV-1-specific cellular cytotoxicity (ADCC) and virus neutralizing activity were detected in the cerebrospinal fluid (CSF) and, as previously reported, in sera of subjects with varying severity of HIV-1 infection, including patients with or without neurologic or psychiatric symptoms. ADCC-mediating antibodies against target cells infected with the HTLV-IIIB strain of HIV-1 were less frequently present in CSF than in sera, 32 and 60%, respectively. The frequency of ADCC-positive CSF was comparable for the different clinical stages of the disease and was apparently not influenced by the presence or absence of neurologic/psychiatric symptoms. Virus-neutralizing activity was tested against HTLV-IIIB and one CSF-derived viral isolate. Serum antibodies neutralized HTLV-IIIB more frequently than the CSF isolate, 53 and 35%, respectively. In contrast, only three (7%) of the CSF specimens contained neutralizing activity to the CSF-derived isolate and none to HTLV-IIIB. Despite an intact blood-brain barrier in many subjects, the serum/CSF ratios of ADCC or neutralizing antibodies were lower than normally expected. This indicates that both ADCC-mediating and virus neutralizing antibodies may be intrathecally synthesized. Whether these antibodies are protective against or contribute to the histopathologic changes in the brain is not known at present.     

The diagnostic values of serum, pleural fluid and urine neopterin measurements in tuberculous pleurisy.

SETTING: Pulmonary department of a medical academy in Ankara, Turkey. OBJECTIVE: Neopterin is a marker of cell-mediated immunity, and it has been demonstrated that neopterin levels of various body fluids could be elevated in tuberculosis. We aimed to investigate diagnostic values of serum, pleural fluid and urine neopterin measurements in tuberculous pleurisy (TP). DESIGN: Serum, pleural fluid and urine neopterin levels were measured in 34 patients with TP and in 29 patients with pleural effusion of non-tuberculous origin as controls. RESULTS: Neopterin levels in serum, pleural fluid and urine (38.28 +/- 14.18 nmol/l, 38.97 +/- 14.18 nmol/l and 759.15 +/- 622.74 micromol/mol, respectively) were significantly higher in patients with TP than those with non-tuberculous pleural effusion (22.57 +/- 6.02 nmol/l, 21.88 +/- 6.90 nmol/l and 343.10 +/- 233.65 micromol/mol, respectively). Pleural fluid neopterin > or =30 mol/l gave the best diagnostic yield, with 85% sensitivity, 93% specificity, 94% positive predictive value, 84% negative predictive value and 89% diagnostic accuracy, although it is not superior to pleural fluid adenosine deaminase determination. CONCLUSION: We have suggested that elevated serum, pleural fluid and urinary neopterin levels in TP with respect to pleural effusions of non-tuberculous origin may reflect activation of cell-mediated immunity and that pleural fluid neopterin measurement may be of value in the differential diagnosis of TP.     

Activation of tumor necrosis factor — α system in HIV-1 infection: Association with markers of immune activation

Summary The relationships between serum levels of soluble tumor necrosis factor receptors (sTNFRs) and other prognostic and immunological parameters in different immunological subgroups of 64 HIV-1 infected patients were studied. In the patient group as a whole, the raised serum levels of sTNFRs were significantly inversely correlated to the numbers of CD4+ and CD8+ lymphocytes and significantly positively correlated with serum levels of neopterin, HIV-1 p24 antigen and the soluble CD8/CD8+ lymphocyte ratio. However, when the patients were classified into three separate immunological subgroups according to the numbers of CD4+ lymphocytes, only serum levels of neopterin were significantly correlated to levels of sTNFRs in all the defined immunological subgroups. These results indicate that HIV-1 infection is associated with a persistent and chronic immune activation in the TNF system manifested by raised serum levels of sTNFRs, which may reflect sustained activation of the immune system particularly in monocytes/macrophages. Further, these results confirm that, when comparing immunological and virological parameters in HIV-1 infection, different results may be obtained in different immunological subgroups of patients.

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Aktivierung des Tumornekrosefaktor-alpha-Systems bei HIV-1 Infektion. Assoziation mit Markern der Immunaktivierung

Zusammenfassung Die Beziehung zwischen den Spiegeln von löslichem Tumornekrosefaktor-Rezeptor (sTNFR) und anderen prognostischen und immunologischen Parametern wurde in verschiedenen immunologischen Untergruppen von 64 HIV-1 infizierten Patienten untersucht. In der Gesamtgruppe bestand eine signifikante, inverse Korrelation zwischen erhöhten sTNFR-Spiegeln und der Zahl CD4+ und CD8+ Lymphozyten sowie eine signifikante positive Korrelation zu den Serumspiegeln von HIV-1 p24-Antigen, Neopterin und dem Quotienten aus löslichem CD8 und CD8+ Lymphozyten. Bei Unterteilung der Patienten nach CD4+ Zahlen in drei verschiedene immunologische Gruppen bestand in allen definierten immunologischen Untergruppen nur noch eine signifikante Korrelation zwischen Neopterin und dem sTNFR-Spiegel. Diese Ergebnisse lassen annehmen, daß die Infektion mit HIV-1 mit einer persistierenden und chronischen Immunaktivierung des TNF Systems einhergeht, die sich in erhöhten Serumspiegeln von sTNFR zeigt und Ausdruck einer Immunaktivierung, vor allem des Monozyten/Makrophagen-Systems ist. Die Ergebnisse bestätigen außerdem, daß sich beim Vergleich immunologischer und virologischer Parameter der HIV-1 Infektion in den verschiedenen immunologischen Untergruppen der Patienten unterschiedliche Ergebnisse herausstellen können.

     

Cerebrospinal fluid and plasma HIV-1 RNA levels and lopinavir concentrations following lopinavir/ritonavir regimen

Our objective was to study the effect of lopinavir/ritonavir on cerebrospinal fluid (CSF) viral load as part of an antiretroviral combination treatment for HIV-1 infected individuals, and to determine the steady-state concentrations of lopinavir in CSF in relationship to plasma concentrations. Paired CSF and plasma samples from 12 antiretroviral-na?ve HIV-1 infected patients starting combination therapy containing lopinavir/ritonavir were collected at baseline, and during treatment at a first follow-up at median 3.0 months (range 2.6-6.0 months), and at a second follow-up at median 12.1 months (range 6.0-16.5 months). Levels of HIV-1 RNA, CD4+ T-cell count, beta2-microglobulin, neopterin, and lopinavir concentration were analysed. In addition, CSF and plasma lopinavir concentrations in 4 patients already on combination therapy including lopinavir/ritonavir were analysed. Nine of 11 patients had undetectable viral load in CSF and 5/11 in plasma at the first follow-up. At the second follow-up 7/7 had undetectable viral load in CSF and 9/9 in plasma. Intrathecal immunoactivation, measured by neopterin and beta2-microglobulin, decreased significantly both in CSF and serum. The total CSF concentrations of lopinavir were of the same order of magnitude as the unbound concentrations in plasma. Lopinavir mean (+/-SD) concentrations were 42.1 (+/-31.5) nM in CSF and 52.7 (+/-25.2) nM unbound in plasma. We found that antiretroviral combination therapy including lopinavir/ritonavir substantially decreases the viral load, both in CSF and plasma, as well as the intrathecal immunoactivation, measured by beta2-microglobulin and neopterin. CSF concentrations of lopinavir were low, but probably sufficient to have a virological effect.     

Negative correlation between blood cell counts and serum neopterin concentration in patients with HIV-1 infection.

Hematopoietic disturbances are common in patients with HIV-1 infection. Recent studies on immune activation markers such as neopterin demonstrate that HIV-1 infection is associated with chronic immune activation. We investigated a possible association between serum neopterin concentrations and blood cell counts (CD4+ T cells, white blood cells, platelets, red blood cells) and hemoglobin and hematocrit in 94 HIV-1-seropositive individuals [52 Walter Reed (WR) stage 1, 31 WR2, one WR5, and 10 WR6]. There were significant negative correlations between neopterin concentrations and CD4+ T cells, hemoglobin, hematocrit and platelets. These correlations were also significant if either only WR1 and WR2 patients or the entire set of data were considered for calculations. Thus, hematological abnormalities are associated with chronic immune activation in patients with HIV-1 infection. Large amounts of neopterin are released by human macrophages on stimulation with interferon-gamma (IFN gamma), and tumor necrosis factor alpha (TNF alpha) further enhances the effect of IFN gamma. Therefore, our data suggest that activated immune cells and specific cytokines such as IFN gamma and TNF alpha are involved inhibiting hematopoiesis.     

Increased urinary neopterin: creatinine ratio as a marker of activation of cell-mediated immunity and oxidative stress in the Iranian patients with multiple sclerosis

Neopterin, a pyrazinopyrimidine compound, is produced by macrophages after induction by interferon gamma (IFN-g) and serves as a marker of cellular immune system activation followed by oxidative stress. The aim of this study was to determine urinary neopterin to creatinine ratio (UNCR) as a surrogate marker of cell-mediated immune activation in multiple sclerosis (MS). Three weekly early morning urine samples were collected from 27 patients with MS and 31 age- and sex-matched apparently healthy subjects. Urinary neopterin and creatinine were determined using reversed phase high-performance liquid chromatography and Jaffe reaction, respectively. UNCR was significantly higher in patients than in healthy controls indicating IFN-g-induced cellular immunity activation and oxidative stress in multiple sclerosis. As a non-invasive method, UNCR determination may be helpful in monitoring disease progression and the effects of therapies, as well.     

Clinical Significance of Serum and Urinary Neopterin Levels in Patients with Various Liver Diseases

Serum and urinary neopterin levels were measured by radioimmunoassay in 120 healthy controls, 16 asymptomatic HBsAg carriers, 12 patients with acute hepatitis, 13 with chronic inactive hepatitis, 35 with chronic active hepatitis, 46 with liver cirrhosis, 18 with hepatocellular carcinoma, and 6 with alcoholic liver disease. Serum and urinary neopterin levels were significantly higher in almost all patients than in normal subjects. Neopterin levels were highest in acute hepatitis and correlated with the results of liver function tests, but did not show this correlation in chronic liver disease. In chronic liver disease, the levels of serum neopterin in non-A non-B viral patients was significantly increased, compared with those in B viral and alcoholic patients. The rate of abnormal urinary neopterin levels in chronic liver disease was higher than the rate of abnormal serum neopterin levels, but no difference was observed between the rates of abnormal serum and urinary levels in acute hepatitis and asymptomatic HBsAg carriers. These results indicate that serum and urinary neopterin levels may be useful markers for cell-mediated immunity in liver disease, and that the immune system response in chronic liver disease may be different for different pathogens.     

Time-course of neopterin levels in patients suffering from severe sepsis treated with and without Drotrecogin-alpha (activated)

Neopterin is secreted by activated monocytes/macrophages upon stimulation with interferon-gamma. The release of this pro-inflammatory mediator permits the activation status of cell-mediated immune system to be examined. We assayed neopterin plasma concentrations in septic patients under treatment with (n=10) and without Drotrecogin-alpha (activated) (n=10) on d 1 and 6 of severe sepsis. In septic patients treated with Drotrecogin-alpha (activated), neopterin levels decreased significantly (p=0.027) from d 1 (baseline) (mean 140.8 nmol/l, +/-standard error of mean (SEM) 106.2) to d 6 (mean 68.9 nmol/l, +/-SEM 46.4). In patients not treated with Drotrecogin-alpha (activated) there was no significant (p=0.96) decrease of neopterin levels from d 1 (mean 147.8 nmol/l, +/-SEM 58.4) to d 6 (mean 139.7 nmol/l, +/-SEM 52.6). Furthermore, neopterin levels showed significant correlations with bilirubin in all patient groups on d 1 of severe sepsis (range of correlation coefficient, r: 0.69-0.88; p<0.05). Neopterin levels correlated significantly with creatinine with regard to all patient groups (range of correlation coefficient, r: 0.73-0.92; p<0.05). In conclusion, Drotrecogin- alpha (activated) was associated with a significant decrease of neopterin plasma levels in septic patients. Neopterin concentrations appear to depend on renal function and enterohepatic circulation.     

Serum neopterin is elevated in patients infected with Shigella

Background

Neopterin is produced by human macrophages/monocytes when stimulated with interferon-gamma. Production of neopterin is found in serum, cerebrospinal fluid (CSF) and urine of patients with infections by viruses, intracellular bacteria and parasites, autoimmune diseases, malignant tumors and patients in allograft rejection episodes.

Methods

In this study, the level of neopterin was determined in serum samples obtained from patients infected with Shigella (all four species) and healthy individuals. The study population comprised of 14 patients infected with Shigella and 14 normal controls. Serum neopterin was measured using an enzyme-linked immunosorbent assay (ELISA).

Results

The mean of serum neopterin concentration was 36.32 ± 9.71 nmol/L among patients infected with Shigella and 2.88 ± 0.77 nmol/L in the control group. The mean serum neopterin levels were significantly higher in the test group as compared to the normal group (p = 0.002).

Conclusion

This study revealed that neopterin was elevated in patients infected with Shigella.     

The role of serum neopterin level in the evaluation of activation and response to treatment in the patients with pulmonary tuberculosis

Neopterin is an important parameter showing cell mediated immunity activation. In this study we aimed to determine whether serum neopterin level could be used as a marker in the evaluation of tuberculosis activation and response to treatment. The study comprised 40 new case smear positive pulmonary tuberculosis patients and 40 healthy control. Serum neopterin levels were measured both before the treatment and 2nd month of the treatment in the patient group. The association between serum neopterin level and clinical, radiological and bacteriological parameters were also investigated. In patients with pulmonary tuberculosis the mean levels of serum neopterin were 35.1+/-13.4 nmol/L before the treatment and 21.2+/-10.4 nmol/L in the 2nd month of the treatment. In the control group, serum neopterin level was 19+/-10.4 nmol/L. The serum neopterin levels of the patients were significantly higher than the control group (p=0.001). Also, there was significant difference between serum neopterin levels before the treatment and the 2nd month of the treatment (p=0.000). Serum neopterin level was higher in the group with extensive disease than the cases with limited disease (p=0.02). In conclusion, we think that serum neopterin level might be used as a reliable immunological marker in the evaluation of tuberculosis activation and response to treatment.     

Serum and salivary neopterin and interferon-gamma in primary Sjögren's syndrome. Correlation with clinical,laboratory and histopathologic features

OBJECTIVE: To investigate serum and salivary neopterin and interferon-gamma as possible markers of immune system activation in primary Sj?gren's Syndrome (pSS). METHODS: Serum and salivary neopterin and interferon-gamma concentrations were determined in 30 untreated patients with pSS and matched with several other clinical and laboratory parameters. RESULTS: The mean concentration of neopterin was significantly higher in pSS patients (8.12+/- 3.36 nmol/L in serum and 9.50 +/-7.61 nmol/L in saliva) than in normal controls (p<0.05). Significant correlations were found between serum neopterin and beta2-microglobulin, serum IgG as well as lip biopsy score. Salivary neopterin concentration was inversely related to Shirmer-I test, tear break-up time and stimulated salivary flow rate. Serum and salivary levels of interferon-gamma were normal and no correlation with the other parameters was found. CONCLUSION: In pSS patients serum neopterin may represent a useful marker of cell-mediated immunity. On the other hand, salivary neopterin seems to reflect theglandular damage.