Predictive Role of Neutrophil Gelatinase-Associated Lipocaline in Donor-Specific Antibody-Positive and Donor-Specific Antibody-Negative Renal Transplant Patients.

BACKGROUND: Renal transplantation is the best choice for the treatment of dialysis patients with end-stage renal failure because it provides better quality of life and more life time. However, despite successful surgical techniques, immunological issues in kidney transplantation are not completely resolved. Thus, after transplantation, patients must be followed up closely. Although patient follow-up with the use of creatinine and renal biopsy are common, it is thought that biopsy is too invasive and that creatinine is unreliable. Hence, new parameters that correlate with the patient's immunological condition are needed in clinical monitoring. METHODS: One of the biomarkers that has been studied recently is neutrophil gelatinase-associated lipocalin (NGAL). Its diagnostic value in cases of acute renal failure, delayed graft function, and IgA nephropathy is widely investigated. However, data are insufficient as to whether NGAL can be used for follow-up in the chronic process after renal transplantation. We aimed to investigate the predictive value of NGAL in terms of rejection in donor-specific antibody (DSA)-positive and DSA-negative renal transplant patients. Ninety patients were included. RESULTS: We found that rejection rates were higher in patients whose NGAL values were ≥ 50 and DSA-positive. Delayed graft function was seen more frequently in patients whose NGAL values were ≥ 50. CONCLUSIONS: An increase in NGAL level does not always indicate renal injury because NGAL is also an acute-phase reactant. NGAL cannot be used alone to diagnose rejection, but, if NGAL level is high, it is necessary to study DSA, and sub-clinical rejection must be researched.

Kidney transplantation in immunologically high-risk patients.

An increased number of sensitized patients await kidney transplantation (KTx). Sensitization has a major impact on patient mortality and morbidity due to prolonged waiting time and may preclude live donor transplantation. However, recent reports have shown that KTx can be performed successfully using novel immunosuppressive protocols. This study presents our experience with patients displaying donor-specific antibody (DSA) (+). We enrolled 5 lymphocyte cross-match (LCM) negative (complement-dependent cytotoxicity) and panel-reactive antibody (PRA) plus DSA-positive patients mean fluorescein intensity [MFI] > 1000) who underwent living kidney donor procedures. All subjects were females and their mean age was 36.7 years. In our protocol, we started mycophenolate mofetil (2 g/d), tacrolimus (0.01 mg/kg) and prednisolone (0.5 mg/kg) on day -6. We performed 2 sessions of total plasma exchange (TPE) with albumin replacement and administered 2 doses of IVIG (5 g/d). On day -1, we added rituximab (200 mg). On the operation day and on day +4, the patients received doses of basiliximab. Serum samples were taken on days -6, 0, and 30 as well as at 1 year after transplantation. All patients displayed immediate graft function. Mean basal DSA titer was 5624 MFI. After desensitization, the MFI titers decreased at the time of transplantation to 2753 MFI, and were 2564 MFI at the 1st month and 802 MFI at 1st year. Three patients experienced acute rejection episodes (60%). After treatment for rejection, the average follow-up was 17 months and last creatinine levels were 0.6-0.8 mg/dL (minimum-maximum). In conclusion, KTx can be succesfully performed in sensitized patients displaying DSA. However, there seems to be a greater acute rejection risk. There is no consensus regarding adequate doses of IVIG or plasmapheresis treatments; furthermore, more studies are needed to clarify the safe MFI titer of the DSA.

Cytotoxic T lymphocyte-associated antigen-4 polymorphism in patients with rheumatic heart disease.

Acute rheumatic fever (ARF) is a systemic inflammatory disease occurring as a consequence of an exaggerated immune response to group A, beta haemolytic streptococcal pharyngitis. The molecular mimicry between human target organs/tissues and specific components of the infectious organism leads to the development of autoimmune reactions and cardiac tissue damage in rheumatic heart disease (RHD). Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation and proliferation during the immune response. CTLA-4 gene polymorphism has been shown to affect the inhibitory function of CTLA-4. We aimed to analyze the association of CTLA-4 gene locus at position 49 of exon 1 with susceptibility to ARF/RHD. This study included a total of 98 patients with RHD as a sequela of ARF, who fulfilled the revised classification criteria of Jones and 154 healthy unrelated controls. CTLA-4 +49 A/G polymorphism was genotyped by using PCR-RLFP technique. Data was analyzed by binary logistic regression models. The frequencies of GG, GA and AA genotypes were found to be 14%, 47% and 39%, respectively, in patients and 6%, 45% and 49%, respectively, in controls. The GG genotype was found to be significantly different between patients and controls (OR: 3.11; P = 0.016). GA and AA genotypes did not statistically differ between patients and controls. Our data showed a significant association of +49G /G polymorphism in a small patient group with RHD.

Thymidylate synthase genotype and serum concentrations of homocysteine and folate in Behçet's disease.

The aim of this study was to assess whether thymidylate synthase (TYMS) genotype, serum homocysteine, and folate concentrations were related to venous thrombosis in Behçet's disease (BD) patients. The study included 104 BD patients fulfilling the International Study Group Criteria for the diagnosis of BD and 121 healthy individuals-controls. Out of 104 patients, 50 (48%) had vascular involvement: 34 had active-history of venous thrombosis, 16 had arterial involvement (aneurysm), and 11 of these patients had both venous and arterial lesions as confirmed by Doppler ultrasound and/or angiography. Genotype analysis of the TYMS promoter enhancer region was determined by polymerase chain reaction. The distribution of the TYMS genotypes 2R/2R, 2R/3R, 3R/3R, 4R/2R, and 3R/3R were not significantly different between BD patients and control group (p>0.05; 16.5% vs 8.3%, 49.0% vs 53.9%, 31.7% vs 38.0%, 1.9% vs 0%, and 1.0% vs 0%, respectively). TYMS genotypes were not associated with thrombosis and serum homocysteine concentration in BD patients. The mean serum homocysteine level in patients with thrombosis (14.87+/-8.99 micromol/L) was significantly higher than the level in patients without thrombosis (10.78+/-3.81 micromol/L; p<0.05). Serum folate concentrations were not different between the BD patients and the healthy controls. The study results suggest that the distribution TYMS genotype in BD was not different from that of healthy controls. There was no relationship between TYMS genotype and the homocysteine levels in BD patients with thrombosis or without thrombosis.

Circulating endothelial cells in preeclampsia.

Endothelial dysfunction plays an important role in the pathogenesis of preeclampsia. Increased number of circulating endothelial cells (CECs) have previously been reported after various diseases associated endothelial injury. The aim of this study was to evaluate the CECs in patients with preeclampsia and to demonstrate any association between CECs and homocysteine, which is another marker of vascular injury. The study included 20 preeclamptic, 15 hypertensive women, 15 healthy pregnant and 15 healthy non-pregnant women. All subjects had normal renal function. Systolic and diastolic blood pressures, serum homocysteine levels were measured. To isolate CECs, peripheral blood was first incubated with anti-CD-146 antibody and subsequently conjugated to immunomagnetic beads. Cells were stained with acridine and counted. Preeclamptic patients had elevated numbers of CECs (13.2+/-5.2 cells/ml) compared with hypertensive patients (6.9+/-0.8 cells/ml), healthy pregnants (5.2+/-1.4 cells/ml), and non-pregnant controls (4.0+/-1.8 cells/ml), (P<0.0001). Serum homocysteine level in preeclamptic patients (9.5+/-2.8 micromol/l) was significantly higher compared with healthy pregnants (6.0+/-0.6 micromol/l), was not different from hypertensive patients (11.5+/-2.3 micromol/l, P>0.05), but it was lesser compared with non-pregnant controls (12.2+/-3.3 micromol/l, P<0.0001). Also, significant correlation between CECs and systolic blood pressure (P<0.0001, r=0.63), diastolic blood pressure (P<0.0001, r=0.64) and serum homocysteine (P<0.01, r=0.55) levels were found in preeclamptic patients. CECs as a marker of endothelial injury were significantly higher in patients with preeclampsia than in hypertensive patients, healthy pregnants and normal controls. Further studies are needed for the prognostic and potential importance of CECs in preeclampsia.

Serum soluble Fas levels in patients with autoimmune rheumatic diseases.

OBJECTIVE: The role of the serum soluble Fas (sFAS) system is unclear in diagnosis of several autoimmune rheumatic diseases although there are present contradictory reports on the levels of serum sFas. We therefore assessed levels of sFAS in serum of patients with autoimmune rheumatic diseases. PATIENTS AND METHODS: We analyzed sFas levels and their relationship to clinical and laboratory data in patients with systemic lupus erythematosus (SLE, n=32), rheumatoid arthritis (RA, n=28), Sjögren's syndrome (SS, n=20) systemic sclerosis (SSc, n=21), polymyositis/dermatomyositis (PM/DM, n=15). Patients with osteoarthritis (OA, n=20) and healthy volunteers (n=20) were used as controls. Serum levels of sFAS were determined by ELISA. sFas levels greater than mean (normals)+2 SD were considered as elevated. RESULTS: The mean sFas values were found higher in RA, PM/DM and OA than in control although no differences were found in SSc and SS patients. The mean sFas levels in SLE patients were lower than healthy controls. Elevated sFas rates in RA, PM/DM and SS were found to be 21.4%, 60%, 10% higher than in healthy controls, respectively. sFas levels in SLE and SSc did not differ from control values. Mean sFas levels did not show significant difference between active and inactive patients in all disease groups except PM/DM, RA and OA. No correlations of sFas with relevant disease subsets, laboratory findings and treatment modalities were found. CONCLUSIONS: The findings indicate that the serum sFas molecule may provide a useful additional marker for presence and assessment of disease in patients with RA and PM/DM.

Genetic susceptibility to rheumatic heart disease and streptococcal pharyngitis: association with HLA-DR alleles.

Acute rheumatic fever (ARF) is a systemic inflammatory disease that develops as a consequence of an exaggerated immune response to group A beta-haemolytic streptococci, which causes pharyngitis. Major manifestations of ARF include carditis, arthritis and chorea. Several investigators have attempted to establish a relation between ARF and human leucocyte antigens (HLA). Heterogeneity in various studies has been found, although associations with certain antigens were reported. The aim of this study was to analyse whether HLA-DR alleles play a role in the resistance or susceptibility to streptococci-related disorders including rheumatic heart disease (RHD) as a sequela of ARF and recurrent streptococcal pharyngitis in Turkish patients. The study included 102 patients with RHD, 71 persons with recurrent streptococcal pharyngitis and 130 healthy controls. HLA-DR alleles were typed by using polymerase chain reaction (PCR)-sequence-specific primers. Positive association with HLA-DRB1*07 allele was found for RHD when compared with healthy controls [29.4% vs 13.1%; P < 0.01, P-corrected: P < 0.01, odds ratio (OR) 2.78, 95% confidence interval (CI) 1.43-5.26] and also for recurrent streptococcal pharyngitis (26.8% vs 13.1%; P < 0.05, P-corrected: P < 0.05, OR 2.44, 95% CI 1.17-3.56). The frequency of HLA-DRB1*11 allele was decreased in patients with RHD (23.5% vs 42.3%; P < 0.01, P-corrected: P < 0.01, OR 0.42, 95% CI 0.24-0.75). Data suggest that HLA-DRB1*07 allele may be a genetic factor in increasing the susceptibility to develop RHD and recurrent streptococcal pharyngitis. HLA-DRB1*11 allele seems to be a protective factor against RHD.

The effects of calcitriol therapy on serum interleukin-1, interleukin-6 and tumour necrosis factor-alpha concentrations in post-menopausal patients with osteoporosis.

Seventy post-menopausal women with osteoporosis were randomized into two groups: 40 patients received calcitriol (0.5 microg/day) and calcium (1000 mg/day); and 30 control patients received calcium (1000 mg/day) alone. Thirty healthy women formed the healthy control group. Bone mineral density (BMD) and serum interleukin (IL)-1, IL-6 and tumour necrosis factor-alpha (TNF-alpha) concentrations were measured at baseline and after 6 months of treatment. Calcitriol treatment for 6 months significantly increased BMD and reduced serum IL-1 and TNF-alpha concentrations compared with no significant changes in patients treated with calcium alone. Both treatments increased serum calcium and decreased parathyroid hormone concentrations. The healthy control group had a significantly lower IL-6 concentration than the post-menopausal women with osteoporosis. We have shown that calcitriol was an effective treatment for osteoporosis. Significant reductions in serum IL-1 and TNF-alpha concentrations suggest that, in addition to increasing the absorption of calcium, calcitriol may directly affect bone metabolism via cytokines.

Serum soluble CD30 levels in Behçet's disease.

Behçet's disease is associated with the inflammatory response. Several reports indicate the presence of primarily CD4+ T cells of the Th1 subtype in the inflammation process of the disease. Serum soluble CD30 (sCD30) is reported to be released from CD4+ Th2 type cells and has been suggested to be a marker of Th2 activity. In this study, serum sCD30 levels were measured in active and inactive patients with Behçet's disease, healthy controls and a group of patients with rheumatoid arthritis, typical Th1 disorder using enzyme immunoassay kit. Mean sCD30 value of 54 active patients were found significantly higher than in those of 17 inactive patients (p = 0.027), 20 healthy controls (p = 0.040) and 25 patients with rheumatoid arthritis (p < 0.001). There was a significant correlation between increased sCD30 levels and clinical activity index in active patients with Behçet's disease. High serum levels of sCD30 may reflect the activation of CD4+ T cells or a subset of them in active BD patients. In addition to serum sCD30 levels, measurements of the Th2 cytokines may be a helpful tool for the evaluation of Th2 activity in Behçet's disease.

[Human leukocyte antigens A and B in Turkish patients with sarcoidosis]. / Antígenos leucocitarios humanos A y B en pacientes turcos con sarcoidosis.

OBJECTIVE: Associations between human leukocyte antigens (HLA) and sarcoidosis have been reported in several studies. We aimed to investigate these associations in Turkish patients. PATIENTS AND METHOD: We performed HLA-A, HLA-B, HLA-C, and HLA-D typing in 83 patients with sarcoidosis and in 250 healthy controls using a microlymphocytotoxicity method to investigate genetic susceptibility to the disease. RESULTS: Because of significant violation of Hardy-Weinberg equilibrium at HLA-C and HLA-DQB1 loci, only results obtained at other HLA loci were used. Although HLA-A9, HLA-B5, and HLA-B8 allele frequencies were significantly higher in the patient group compared to the controls (odds ratio [OR]= 21.8, P= .015; OR= 9.34, P= .049; OR= 2.26, P= .031, respectively), none of the differences remained significant after applying the Bonferroni correction. HLA-A24, HLA-A26, and HLA-B62 alleles were significantly less frequent in the patient group compared to the controls (OR= 0.48, P= .018; OR= 0.19, P= .003; OR= 0.11, P= .044, respectively). However, the differences also failed to remain significant after Bonferroni correction. CONCLUSIONS: These results suggest that both HLA may play significant roles (either increasing or reducing risk) in the pathogenesis of sarcoidosis and in its distinct clinical forms and laboratory findings.

Adenosine deaminase activity in bronchoalveolar lavage in Turkish patients with smear negative pulmonary tuberculosis.

The sputum smear-negative patients have been a diagnostic challenge for health professionals. Adenosine deaminase (ADA) activity has been shown to rise in various body fluids of patients with tuberculosis (Tb). A prospective clinical trial was conducted to determine the diagnostic value of ADA activity in bronchoalveolar lavage (BAL) in sputum smear-negative subjects highly suggestive for pulmonary Tb. Nineteen (M/F: 15/4, mean age 46.8 +/- 16.5 years) sputum smear-negative patients highly suggestive for pulmonary Tb constituted Group I. Acid fast bacilli (AFB) grew on sputum and/or BAL culture of all subjects in this group. Twenty-nine patients (M/F: 19/10, mean age 55.7 +/- 8.0 years) with non-tuberculous pulmonary diseases constituted Group II. Ten of them had interstitial lung disease, nine lung cancer, five pneumonia and five COPD. Twelve subjects (M/F: 7/5, mean age 48.4 +/- 12.8 years) constituted the controls (Group III) undergoing fiberoptic bronchoscopy (FOB) for various indications and the lungs were found to be normal eventually. Albumin and ADA activity levels were measured in plasma and BAL in all the subjects. LocalADA was calculated. PlasmaADA and BALADA of Group I was significantly higher (P < 0.001) than that of the other groups. LocalADA was also the highest in Group I when compared with the others (P < 0.001) but that of Group II was also higher (P < 0.01) when compared with controls. With a cut-off value derived from the control subjects, sensitivity of BALADA was 100% and specificity 85.3%. Sputum PCR results are available in a couple of days whereas that of BALADA are available in a couple of hours and BALADA costs cheaper than PCR in our country. Therefore, we conclude that BALADA may be a useful, cheaper and faster diagnostic test in sputum smear-negative patients highly suggestive for pulmonary Tb. LocalADA need not be calculated as it is also significantly higher in Group II subjects and thus not as reliable as BALADA.

Association of psoriasis vulgaris with HLA class I and class II antigens in the Turkish population, according to the age at onset.

BACKGROUND: Association of psoriasis vulgaris with HLA antigens reference to age at onset has been reported in different racial or ethnic populations. OBJECTIVE: Our purpose was to determine the distribution of HLA markers in the Turkish population according to the age at onset of the psoriasis vulgaris. METHODS: HLA class I and class II antigens were performed by serologic methods in a group of 100 Turkish patients with psoriasis and 201 control subjects. Patients with psoriasis were subdivided into two groups based on age at onset (below or above 40 years of age) and family history. RESULTS: The frequency of HLA A30, Cw3, Cw6, DR7, DR14, DQ8, and DQ9 antigens were significantly increased in the Turkish psoriatic patients whereas HLA A66, Cw2, Cw4 and DR11 were found to be negatively associated with psoriasis. However, there were striking differences in HLA antigens according to the age at onset of the disease. Type I, early onset was associated with a high frequency of A30, B50, Cw6 and DR7 antigens whereas patients with type II, late onset had an increased frequency of Cw7. CONCLUSIONS: We conclude that psoriasis is probably a genetically determined disease and suggest that HLA-Cw6 antigen seems to associate commonly with early onset of psoriasis in Turkish patients.

Effect of losartan on circulating TNFalpha levels and left ventricular systolic performance in patients with heart failure.

BACKGROUND: Tumor necrosis factor alpha (TNFalpha) plays an important role in the pathophysiology of heart failure. Recent studies have shown a beneficial effect of losartan in these patients. However, the effect of losartan on TNFalpha levels in heart failure has not yet been studied. We evaluated the effect of losartan on circulating TNFalpha levels and ejection fraction (EF) in patients with congestive heart failure. METHODS: Forty patients with heart failure and EF < or = 40% were enrolled into the study. All of the patients have been given diuretic and digitalis therapy. Twenty patients were given losartan (50 mg/d) (Group I, 10 women, 10 men, 12 dilated cardiomyopathy, 8 ischemic heart disease, mean age 64.9 + 8.9), and another 20 patients were not given losartan because of hypotension or renal dysfunction (Group II, 13 men, 7 women, 10 dilated cardiomyopathy, 10 ischemic heart disease, mean age 61.2 +/- 10.5). EF was measured at the initial evaluation and on the fifteenth day of the therapy by echocardiographic examination using an acoustic quantification method. Circulating TNFalpha levels were also measured at the initial evaluation and on the fifteenth day of therapy by the ELISA method. RESULTS: Losartan significantly increased EF and decreased TNFalpha (EF increased from 29.4 +/- 7.3% to 36.0 +/- 8.5%, P < 0.001, and TNFalpha decreased from 39.2 +/- 37.4 pg/ml to 27.0 +/- 30.0 pg/ml, P < 0.05). Changes in TNFalpha levels and EF were not found to be correlated (r=-0.28, P=0.24). However, in the control group, EF and TNFalpha levels were similar at baseline and at the fifteenth day (EF 31.4 + 8.1% vs 31.7 +/- 7.8%, P=0.1, and TNFalpha 91.5 + 86.0 pg/ml vs 110.0 +/- 80.7 pg/ml, P=0.1, respectively). CONCLUSIONS: Losartan improves left ventricular systolic function and decreases TNFalpha level. The decreased TNFalpha level seems to be independent of EF.

Thiemann's disease: a case report.

In this case report, we describe a patient with the diagnosis of Thiemann's disease, which is a genetically determined rare form of idiopathic avascular necrosis of the proximal interphalangeal joints of the hands.

Soluble intercellular adhesion molecule-1 (sICAM-1) in patients with allergic rhinoconjunctivitis.

Intercellular adhesion molecule-1 (ICAM-1), a member of immunoglobulin supergene family with a five-domain structure, is known to play an important role in inflammatory disease. We measured levels of soluble ICAM-1 in sera of 25 patients with allergic rhinoconjunctivitis (7 male, 18 female: age range 14-47 years, mean 29.8 +/- 9.2) and 20 healthy subjects (11 male, 9 female: age range 22-48 years, mean: 33.3 +/- 7.6). All allergic patients had positive history, positive skin prick test and conjunctival provocation test, and radioallergosorbent test for specific allergens. Soluble ICAM-1 in serum samples was determinated by ELISA. The mean serum sICAM-1 levels, in healthy subjects was 193.3 +/- 68.8 ng/ml and in patients with allergic rhinoconjunctivitis was 212.6 +/- 50.9 ng/ml. There were no difference in sICAM-1 levels in both of the groups (P > 0.05). In male patients with allergic rhinoconjunctivitis, sICAM-1 levels (mean: 234.5 +/- 55.0 ng/ml) were higher compared to female patients with allergic rhinoconjunctivitis (mean: 204.1 +/- 48.1 ng/ml) and control group (P < 0.05 and P < 0.05 respectively). Soluble ICAM-1 levels were high in patients with allergic rhinoconjunctivitis who had high level of symptom score.

The early effect of specific immunotherapy on lymphocyte response to PHA and allergens in atopic patients with allergic rhinitis.

In the first part of this study, peripheral lymphocyte subpopulations and their proliferative response to PHA and allergens were investigated in the 30 patients with allergic rhinitis compared to 20 healthy non-atopic individuals. Data obtained employing a PHA-induced lymphoproliferative response assay revealed that the allergic rhinitis generated significantly less activity than did the normal control group. Significantly decreased ration of CD4+/CD8+ T cells was noted in the patients with allergic rhinitis. Mean values of stimulation indices by allergen extracts were higher in the patients sensitive to same antigen than others especially in concentration of 1000 SQU/ml. Stimulation of active lymphocytes revealed no statistically significant group differences between allergens. In the second part of the study, the early effect of immunotherapy on T cell subsets and lymphocyte proliferative response to PHA and allergens were examined in the peripheral blood lymphocytes of patients. A significant increase in PHA-induced and in allergen induced lymphoproliferative response were observed in all patients after sixth months of immunotherapy. It is concluded that there may be an association between allergic rhinitis and deficiency of circulating CD4+ cells but further studies are required to substantiate this hypothesis.

Soluble intercellular adhesion molecule-1 (sICAM-1) in patients with systemic lupus erythematosus.

Circulating sICAM-1 is known to be elevated in various inflammatory disorders. It is further suggested that elevated levels correlate well with disease activity in several autoimmune disorders. The objectives of this study are to determine the serum sICAM-1 levels in patients with systemic lupus erythematosus (SLE) and correlate sICAM-1 levels with clinical and laboratory (ESR, CRP, anti-dsDNA) measures of disease activity. Forty-one patients (34 female, 7 male) all fulfilling 1982 ARA classification criteria for SLE and 16 healthy controls (8 female, 8 male) were included in the study. Disease activity was measured according to SLEDAI. sICAM-1 was determined by ELISA. Mean sICAM-1 in SLE patients (339 +/- 161 ng/ml) were significantly higher than in the controls (216 +/- 85 ng/ml) (p < 0.005). Although slightly elevated in active patients, there was no statistically significant difference between mean sICAM-1 levels of active and inactive SLE patients (349 +/- 183 ng/ml and 316 +/- 103 ng/ml respectively) (p > 0.05). We could not find a correlation between sICAM-1 levels and any organ involvements. Similarly, no significant correlation was found between ESR, CRP, anti-ds-DNA and sICAM-1. These results suggest that although higher than normal, sICAM-1 levels in SLE do not provide additional information over conventional activity markers.

Evaluation of interleukin-6 in rheumatoid arthritis as an activity criterion.

This study evaluated interleukin-6 levels as an activity criterion in rheumatoid arthritis (RA) and compared if with other activity criteria. We evaluated 35 patients with active RA, 31 with inactive RA, and 25 patients with osteoarthritis, in addition to 28 healthy individuals. Serum interleukin-6 levels were higher in active RA patients than in those with inactive RA, or osteoarthritis and healthy individuals (P < 0.001). Serum interleukin-6 levels of patients with active RA were positively correlated with the erythrocyte sedimentation rate, C-reactive protein, and alpha 2-globulin levels (P < 0.001), but there was a negative correlation with serum albumin levels (P < 0.05). We conclude that interleukin-6 can be responsible for both the most systemic manifestations of RA and for its local manifestations.

Fibronectin and circulating immune complexes in Behet's disease.

Being a high-molecular-weight adhesive glycoprotein, fibronectin (Fn) is suggested to be a component of immune complexes and may participate in the clearance of immune complexes. In Behçet's disease (BD), a multisystem disorder of unknown etiology, immune complexes have been shown to be deposited in affected tissue during disease activity, suggesting an immune mechanism. This study investigates the relationship between Fn and circulating immune complexes (CIC) and evaluates the changes in the levels of Fn and CIC along with disease activity. In 63 patients (31 active, 32 inactive) with BD, plasma Fn and serum CIC, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and the third and fourth components of the complement system (C3, C4) were studied. The mean ESR, CRP, C3 and C4 levels of active BD patients were found to be significantly higher than those of the inactive BD patient group. Although the mean Fn and CIC levels of BD patients were not significantly different from those of the healthy control group, Fn and CIC values of active BD patients were significantly lower than in the inactive group. Moreover, no significant correlation was observed among Fn levels and ESR, CRP, C3, C4 and CIC levels in BD patients. The result of this study suggest that the variation in Fn concentration is independent of the acute-phase response. The lack of relationship between the CIC and Fn concentrations indicates that IC deposition in the vessel wall is independent of the CIC levels. In order to determine the exact roles of Fn and IC, further studies in tissue specimens are required.