Soluble CD4 in patients with rheumatoid arthritis and osteoarthritis

An ELISA was used to measure the soluble form of the leukocyte surface antigen CD4 (sCD4) in the sera and synovial fluids (SF) of patients with rheumatic diseases. Patients with rheumatoid arthritis (RA) had raised levels of sCD4 in both their sera and synovial fluid compared to age-matched healthy controls. In patients with osteoarthritis levels of sCD4 in SF and sera were lower than in RA but higher than in sera of healthy individuals. Mononuclear cells from the synovial fluid of RA patients were found to produce spontaneously high levels of sCD4, but autologous blood cells only produced comparable levels after in vitro stimulation with mitogenic lectin. In individual RA patients with active disease, serial sCD4 levels fell preceding clinical improvement. In three patients where serum sCD4 levels fell and clinical improvement occurred, subsequent small increases in serum sCD4 preceded increased clinical disease activity by up to 5 days. Synovial fluid levels of sCD4 correlated positively with soluble interleukin 2 receptor levels but no correlation was found with sCD8 levels. We conclude that the release of sCD4 reflects the involvement of T helper cells and macrophages in the pathogenesis of joint inflammation, especially in RA.     

Characterization of a soluble form of CD58 in synovial fluid of patients with rheumatoid arthritis (RA)

Reduced levels of a soluble form of the adhesion receptor and CD2 ligand CD58 (sCD58) were previously described in RA patients. In order to understand the biological significance of this finding we biochemically characterized sCD58 in RA and asked how well sCD58 binds to CD2. sCD58 concentrations were measured in serum and synovial fluid (SF) samples of RA patients by two ELISAs, one detecting domain 1 of CD58 (CD58-D1), and the other one the complete molecule (CD58-D1 + D2). Small amounts of split sCD58-D1 were found in most RA sera, but not SF. In addition, split sCD58-D2 was detected in SF by affinity chromatography, SDS–PAGE, and Western blotting. Gel filtration gave similar peaks at 95–125 kD for RA sera, SF, and normal serum. Binding of SF-sCD58 to the CD2⁺ Jurkat variant JBB1 or recombinant CD2 was stronger than urinary sCD58 and reached binding of oligomeric recombinant CD58 at low concentrations. In conclusion, sCD58-split products were found in RA sera and SF. At concentrations as they occur in vivo, SF-sCD58 binds to CD2 much more strongly than urinary sCD58. It is conceivable that locally released sCD58 blocks the CD2/CD58 interaction under physiological conditions. Insufficient release of sCD58, e.g. in synovitis, might result in T cell accumulation and perpetuation of inflammation.     

Levels of the soluble forms of CD80, CD86, and CD83 are elevated in the synovial fluid of rheumatoid arthritis patients

The release of soluble forms of CD80 (sCD80), CD86 (sCD86), and CD83 (sCD83) provide a potentially powerful immunoregulatory mechanism. We therefore investigated the potential presence and relative levels of these molecules in the synovial fluid (SF) and serum of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Serum and SF levels were measured by enzyme-linked immunosorbent assay. Serum levels of sCD80, sCD86, and sCD83 in RA and OA patients were similar to those present in normal donor serum (NDS) and the SF of OA patients. In contrast, when compared with NDS and OA SF levels, almost all RA SF samples had elevated sCD83 levels (32/35, >0.63 ng/ml) and a substantial proportion had elevated sCD80 (13/29, >0.22 ng/ml) or sCD86 (16/33, >2.31 ng/ml) levels. Analysis of matched pairs of serum and SF from RA patients demonstrated that the SF/serum ratio for sCD80 (95% CI = 1.7-3), sCD86 (95% CI = 1.5-3.1), and sCD83 (95% CI = 3.6-7.8) levels was >1 in almost all patients. In conclusion, this study shows that the SF from almost all RA patients contain elevated levels of sCD83 and the majority of these samples also contain elevated levels of sCD80 and/or sCD86. These molecules may play a role in modulating immune responses within the rheumatoid joint.     

Increased synovial fluid levels of soluble CD23 are associated with an erosive status in rheumatoid arthritis (RA)

Synovial fluid (SF) levels of soluble CD23 (sCD23) were determined in 96 patients presenting with an inflammatory knee effusion (73 with RA and 23 with reactive arthritis (ReA) serving as a control inflammatory non-erosive group) and were correlated with the degree of joint destruction, with local immune parameters (IL-1beta, IL-3, IL-4, IL-6, IL-8, IL-10, IL-12 and sCD25) and with serum markers of inflammation, C-reactive protein and erythrocyte sedimentation rate. RA patients, classified as erosive or not according to Larsen's grade, were separated as follows: (i) 13 patients with non-erosive RA; (ii) 16 RA patients with erosions in hands but not in knees, matched for disease duration with the first group; (iii) 44 RA patients with hand and knee erosions, matched with the second group for rheumatoid factor positivity but of longer disease duration. SF sCD23 levels were significantly increased in both erosive RA groups compared with non-erosive diseases, whether RA or ReA (P < 0.05), whose SF levels were not different. SF IL-10 showed a similar profile to that of SF sCD23 and was the only other parameter characteristic of erosive RA, but no direct correlation was found between the two. SF sCD23 was significantly correlated with IL-12 (r = 0.65, P = 0.0001) and sCD25 (r = 0.39, P = 0.0019) exclusively in the two erosive RA populations. In conclusion, these data showing that increased levels of sCD23 are not only found in the SF of erosive joints but also in knee SF of patients with erosive RA but without knee x-ray-diagnosed erosions suggest that this parameter might be of predictive value for joint destruction. Longitudinal studies are however needed to confirm its potential clinical interest.     

Increased levels of beta 2-microglobulin, soluble interleukin-2 receptor, and soluble CD8 in patients with subacute sclerosing panencephalitis.

We measured beta 2-microglobulin (beta 2-M), soluble interleukin-2 receptor (sIL-2R), and soluble CD8 (sCD8) antigen levels in paired cerebrospinal fluid (CSF) and sera from patients with subacute sclerosing panencephalitis (SSPE), multiple sclerosis (MS), and other neurological diseases (OND) using enzyme-linked immunosorbent assay. beta 2-M was significantly increased in CSF of the SSPE group compared to the MS or the OND group. Similarly, beta 2-M in the MS versus OND group was significantly increased in CSF. Although serum levels of beta 2-M were similar in the three groups, the CSF/serum ratios were higher in SSPE versus the MS group and in the MS versus the OND group. Levels of sIL-2R and sCD8 were higher in SSPE CSF than OND CSF; however, there were no differences between levels in SSPE and MS CSF. The levels of sIL-2R were increased in SSPE sera compared to those of MS or the OND group, whereas levels of sCD8 in serum from the three groups were similar. The findings of increased CSF/serum ratio of beta 2-M and higher levels of serum sIL-2R and CSF sCD8 in SSPE patients are consistent with those seen in patients with acute and chronic viral infections. When the levels between the initial and follow-up CSF and serum samples from SSPE patients were compared, the data showed that CSF levels of sCD8 elevated during periods of clinical worsening and decreased during clinical improvement. In contrast, serum beta 2-M decreased during periods of worsening and increased during improvement. The measurement of serum beta 2-M and CSF sCD8 may be useful in SSPE patients as markers to monitor disease activity.     

Modifications of general parameters of immune activation in the sera of Sicilian patients with Boutonneuse fever

The serum levels of β₂-microglobulin (β₂-M), soluble HLA class I antigen (sHLA-I), soluble CD4 (sCD4) and CD8 (sCD8) were studied in 98 Sicilian patients with Boutonneuse fever (BF). In different stages of infection all markers were significantly increased in sera from Sicilian patients with acute BF compared with healthy controls. sCD8 and sHLA-I reached the peak in the second week after the onset of symptoms, whereas sCD4 and β₂-M reached the peak in the first week. Afterwards sCD8 decreased to the levels of controls within the third week, the other parameters decreased later and were unmodified until the third week of infection. Significant correlations were found between sCD4 and sCD8 and the sIL-2R, as well as between serum levels of β₂-M and sCD8. The reduction of CD3⁺ and CD4⁺ and the increase of CD8⁺ T cells in the blood indicate that these cells are involved in the response to rickettsia, and their activation might be in part responsible for the release of sCD4 and sCD8. Our data suggest that these soluble markers, indexes of immune activation of T cells both in the circulation and the affected tissues, may be used in monitoring BF evolution.     

Soluble CD44 splice variants and pelvic lymph node metastasis in ovarian cancer patients

Alternative splicing of CD44 and aberrant levels of soluble CD44 protein in the serum of cancer patients has been correlated to tumor progression and metastasis. To examine the clinical value of CD44 serum levels (sCD44) in ovarian cancer we determined concentrations of the soluble, variable isoforms sCD44std, sCD44v5 and sCD44v6 with a sensitive ELISA. Pre-operative serum samples from 66 patients with histologically diagnosed invasive disease as well as sera taken from 40 healthy blood donors were analyzed. In sera of ovarian cancer patients we detected elevated concentrations of overall CD44 serum levels represented by sCD44std (p=0.001), but decreased levels of the specific isoforms CD44v5 (p=0.0002) and v6 (p=0.0001). This is the first report demonstrating that ovarian cancer patients with pelvic lymph node metastasis at the time of diagnosis showed specifically elevated sCD44v6 (p=0.073) serum concentrations in comparison to patients without lymph node involvement, whereas overall sCD44 serum levels did not differ. Decreased serum levels of sCD44v5 were found in progesterone receptor-positive tumors (p=0. 059) and postmenopausal patients (p=0.032). Increased concentrations of sCD44v6 were detectable in estrogen receptor-positive tumors but not significantly (p=0.138). Serum CD44v5 levels were associated with shortened relapse-free survival time. No association was found between serum CD44 isoforms and the classical clinicopathological parameters stage and grading or overall survival. CD44 splice variants are possibly involved in a complex interaction with the hormonal environment during tumorigenesis and metastasis of ovarian cancer.     

Reduction of soluble complement receptor 2/CD21 in systemic lupus erythomatosus and Sjogren's syndrome but not juvenile arthritis

A soluble form of the complement receptor CD21 (sCD21) is shed from the lymphocyte surface. The amount of sCD21 in serum may modulate immunity as sCD21 levels are correlated with several clinical conditions. We report here the serum levels of sCD21 in juvenile arthritis (JA), systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). Using enzyme-linked immunosorbent assay, we determined sCD21 levels in SLE, SS and JA patients. Mann-Whitney test for nonparametric two-tail P value was performed to obtain statistical significance. Cytometrical analysis of synovial fluid leucocytes of JA patients was done on a FACSsort. While sCD21 levels in SLE and SS are reduced to levels previously found in rheumatoid arthritis (RA), JA sCD21 levels were normal. sCD21 levels did not correlate with clinical parameters and immunophenotype of synovial cells. CD4 T cells in the synovium were almost all of the CD45RO memory type and 13 of 40 patients displayed synovial expansion of gammadeltaT cells. CD21 shedding in JA differs from RA/SS/SLE. JA sCD21 levels in synovial fluid are always lower compared to blood levels of the same patients. Analysis of JA synovial T cells indicates a T-cell driven response.     

Soluble interleukin-2 receptor and soluble CD8 antigen in active rheumatoid arthritis

Concentrations of soluble interleukin-2 receptor (sIL-2R) and of soluble CD8 antigen (sCD8) in sera and in supernatants of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) derived from patients with active rheumatoid arthritis (RA) were studied. sIL-2R concentrations in sera derived from patients with RA (1484 +/- 382 U/ml) were significantly higher than in sera derived from healthy controls (380 +/- 110 U/ml; P less than 0.0005). In contrast, supernatants of PHA-stimulated PBMC derived from patients with RA contained similar amounts of sIL-2R (727 +/- 467 U/ml) as those derived from healthy control individuals (833 +/- 508 U/ml; P greater than 0.1). When investigated for the presence of sCD8 antigen, sera derived from patients with RA contained significantly lower amounts (30 +/- 28 U/ml) than sera derived from healthy controls (405 +/- 136 U/ml; P less than 0.0005). Similarly, PHA stimulation of PBMC derived from patients with RA resulted in a significantly lower production of sCD8 (35 +/- 46 U/ml) as compared to the one obtained by PHA stimulation of PBMC derived from healthy controls (177 +/- 59 U/ml; P less than 0.0005). This difference could not be explained by a lower proliferative response to PHA by PBMC derived from patients with RA (21,474 +/- 14,022 cpm) as compared to healthy controls (29,549 +/- 11,188 cpm; P greater than 0.05). Our data demonstrate that PBMC derived from patients with active RA differ from PBMC derived from healthy individuals concerning their ability to produce sIL-2R and sCD8.     

Elevated levels of soluble CD40 ligand (sCD40L) in serum of patients with systemic autoimmune diseases

The CD40–CD40L costimulatory pathway is involved in the evolution of many autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SS). Increased levels of sCD40L in the serum have been associated with disease activity in SLE. The aim of this study was to investigate the role of sCD40L in the development of lupus nephritis and examine its possible association with cryoglobulinemia in Sjögren's syndrome. We used a 2-site sandwich ELISA to measure the levels of sCD40L in sera, from 64 patients with SLE, RA and SS and 17 healthy blood donors. Biological specimens from the affected tissues such as urine from patients with lupus nephritis and saliva from patients with SS were also tested. In this regard, paired sera and first morning urine samples from 6 SLE patients (3 with active lupus nephritis and 3 with inactive lupus nephritis) were tested with the sCD40L ELISA protocol as well as paired sera and salivary samples from 5 patients with SS and cryoglobulinemia, 5 patients with SS and anti-Ro or anti-La autoantibodies and 5 age-matched healthy control donors. We also examined possible correlations of sCD40L levels with several laboratory and clinical parameters in SS and SLE. We found that sera from SLE and SS patients had significantly higher levels of sCD40L compared to sera from healthy control donors. No sCD40L was detected, in urine samples of patients with either active or inactive nephritis and in salivary samples from SS patients or normal subjects. Soluble CD40L is elevated in sera of SS and SLE patients but further investigation is needed to determine its possible role in SLE nephritis and Sjögren's syndrome.     

Elevation of soluble CD23 in sera from patients with infectious mononucleosis

CD23 is induced in B cells upon infection by Epstein-Barr virus (EBV) and a soluble form (soluble CD23: sCD23) is found in culture supernatants from EBV-transformed B cell lines. Based on these observations, we measured serum sCD23 levels in patients with infectious mononucleosis (IM) caused by EBV infection. Sera from patients with IM at the time of diagnosis contained more sCD23 than sera from normal control subjects. Changes in serum sCD23 levels during the course of disease showed that serum sCD23 levels were elevated at the time of diagnosis and they decreased to the normal levels during the convalescent phase defined by the improvement of symptoms of IM. These results indicate that the elevated levels of sCD23 were observed at the acute phase of IM and may be useful in diagnosing IM. J. Med. Virol. 53:384–387, 1997. © 1997 Wiley-Liss, Inc.     

CD8 serum levels in acute graft-versus-host disease diagnosis

Attempts to identify an early and discriminating marker of acute graft-versus-host disease (aGvHD) have been unsuccessful. The levels of soluble CD4 and soluble CD8 in serum correlate with T cell subset activation and may be important in monitoring and characterizing immunological processes. We determined serum soluble CD4 (sCD4) and sCD8 levels with a two-site sandwich enzyme immunoassay on patients' serum samples collected prior to bone marrow transplantation and weekly after transplantation until day +28. No significant increment of sCD4 was documented in each determination. sCD8 rose significantly before diagnosis or development of maximal clinical symptoms in patients with grade II–III aGvHD than grade 0–I aGvHD [at day +21—median value 447 IU/ml; range 94–713; versus 1136 IU/ml, range 790–1416P=0.002); at day +28—median value 443 IU/ml, range 73–992, versus 1164 IU/ml, range 625–1960P=0.005)]. On the day of marrow infusion the sCD8 levels were significantly higher in patients who subsequently developed grade II–III than in patients with grade 0–I aGvHD (median value 155 IU/ml, range 10–332, versus 350 IU/ml, range 283–830;P=0.003). Careful monitoring of sCD8 is a useful tool for a prompt aGvHD diagnosis and may be used in a clinical bone marrow transplantation setting.     

Evaluation of serum levels of soluble CD4, CD8 and beta 2-microglobulin in visceral human leishmaniasis.

The levels of soluble CD4 (sCD4), sCD8 and beta 2-microglobulin (beta 2-M) were measured in sera from patients with visceral leishmaniasis during the course of infection. Levels of sCD4, sCD8 and beta 2-M were raised significantly above levels in normal sera and returned to the normal range after recovery. The decrease in the levels of sCD8 was related to a reduction of anaemia, leukopenia and thrombocytopenia. In contrast, sCD4 levels fluctuated during the period of infection. beta 2-M returned within normal range more rapidly than sCD8 secretion. Our results suggest that T cells are activated during infection, and that it is also possible that the raised levels of these soluble molecules play a role in the impairment of protective immunity.     

Soluble human leukocyte antigen: a diagnostic indicator of rheumatoid arthritis?

Early stage rheumatoid arthritis (RA) is often difficult to diagnose because initial symptoms are non-specific. To aid diagnosis, suitable serological diagnostic markers are sought. Elevated levels of soluble MHC class II (soluble human leukocyte antigen; sHLA-DR) in human serum have been associated with rheumatoid and 'rheumatoid-like' autoimmune diseases. As a result, sHLA-DR has been suggested as a specific marker of RA. However, reported levels of sHLA-DR in sera of healthy donors vary significantly and the mechanism of release of HLA-DR into serum is poorly understood. Investigations into the diagnostic potential of this molecule necessitate the development of a sensitive and specific sHLA-DR assay. We have investigated multiple ELISA setups to develop such an assay and false positive signal has been carefully removed using a combination of isotype-matched controls and immuno-depletion. sHLA-DR levels in sera of RA patients were not significantly different from those in healthy donors which suggests sHLA-DR has limited utility in the diagnosis of RA. In RA patients, we detected high levels of sHLA-DR in aspirated synovial fluid (SF), but this did not correlate with sHLA-DR levels in serum.     

Patterns of cytokines and soluble cellular receptors in the sera of children with acute chagas' disease

Cytokines and soluble cellular receptors are involved in inflammatory processes and probably in the pathogenesis of parasite and bacterial diseases. In a previous study, we reported increased levels of soluble receptors of interleukin-2 (sIL2-R) in children with acute Chagas' disease, one of the main parasitic infections that is endemic in Latin America. We sought to analyze the pattern of different cytokines and soluble receptors in the sera of children with chagasic infection. Children with acute and indeterminate stages of Chagas' disease, as well as nonchagasic children, were studied. Sera were assayed by enzyme-linked immunosorbent assay to measure the levels of tumor necrosis factor alpha (TNF-alpha), IL-6, IL-2, IL-8, IL-12, sIL-2R, and the soluble receptors of CD8 and CD4 (sCD8 and sCD4). sIL-2R and sCD8 showed the highest levels in serum in acutely infected children, decreasing after specific antiparasite therapy. Chronic children showed a pattern similar to the one of nonchagasic children. Although they were not statistically significant, TNF-alpha, IL-6, and sCD4 showed a tendency to reach high levels in the acutely infected group, whereas IL-2, IL-8, and IL-12 did not reveal changes with respect to the noninfected children. In summary, we report here the patterns of cytokines and soluble receptors in in the sera of children infected with Trypanosoma cruzi; we found significantly increased levels of sIL-2R and sCD8 in acute infection that decreased after therapy, and high levels of TNF-alpha, IL-6, and sCD4 in some of the acute patients. The measurement of sIL-2R and sCD8 may provide a useful tool in the follow-up of children with Chagas' disease.     

Elevated levels of soluble CD8 molecule in patients with lymphatic filariasis

The serum levels of soluble forms of suppressor/cytotoxic cells (sCD8) and interleukin-2 receptor (sCD25) were analyzed in 67 patients with lymphatic filariasis and 28 normal controls. Our results show that patients with lymphatic filariasis have significantly higher levels of sCD8 (p less than 0.05) than the control groups, whereas no such difference was observed for sCD25. Within the patient group, however, those in the chronic lymphatic obstruction (CP) had significantly higher levels of both sCD8 (491 +/- 52 U/ml, p less than 0.001) and sCD25 (293 +/- 36 U/ml; p less than 0.02) than those with asymptomatic microfilaremia (sCD8 344 +/- 32 U/ml; sCD25 190 +/- 10 U/ml, respectively). No statistically significant correlation was observed between the serological levels of sCD8 and the percentage of CD8 on peripheral blood T lymphocytes in any of the patient groups. Evaluation of the activation state of B lymphocyte did not reveal any difference in the cellular expression of B7, or serum levels of soluble CD23 in any of the groups studied. Thus the selective increase of sCD8 in patients with filariasis suggests a possible pathogenic role of the cells involved in the release of this molecule.     

Cyclosporin A (CyA) reduces sCD30 serum levels in atopic dermatitis: a possible new immune intervention

Atopic dermatitis (AD) is a chronic inflammatory skin disease frequently associated with asthma, rhinitis, and food allergy. Lymphocytes producing Th2-type cytokines (such as interleukin [IL]-3, IL-4, and IL-5) have been thought to have a key role in the pathogenesis of the disease. We have recently demonstrated that elevated serum levels of the soluble form of CD30 (sCD30), an activation marker of Th2-cell clones, correlates with disease activity in pediatric patients suffering from AD. Clinical trials have demonstrated that cyclosporin A (CyA) treatment resulted in significant improvement of clinical symptoms in patients affected with AD. In this study, we evaluated the role of CyA in modulating sCD30 release in a group of adult patients affected by severe AD treated with CyA at the dosage of 3.5 mg/kg body weight for 12 weeks. Our results demonstrated, in parallel with an improvement of clinical symptoms, a significant reduction of serum levels of both IL-4 and sCD30, thus suggesting that CyA can prevent the activation of Th2 cells observed in AD.     

Patterns of Cytokines and Soluble Cellular Receptors in the Sera of Children with Acute Chagas' Disease

Cytokines and soluble cellular receptors are involved in inflammatory processes and probably in the pathogenesis of parasite and bacterial diseases. In a previous study, we reported increased levels of soluble receptors of interleukin-2 (sIL2-R) in children with acute Chagas' disease, one of the main parasitic infections that is endemic in Latin America. We sought to analyze the pattern of different cytokines and soluble receptors in the sera of children with chagasic infection. Children with acute and indeterminate stages of Chagas' disease, as well as nonchagasic children, were studied. Sera were assayed by enzyme-linked immunosorbent assay to measure the levels of tumor necrosis factor alpha (TNF-α), IL-6, IL-2, IL-8, IL-12, sIL-2R, and the soluble receptors of CD8 and CD4 (sCD8 and sCD4). sIL-2R and sCD8 showed the highest levels in serum in acutely infected children, decreasing after specific antiparasite therapy. Chronic children showed a pattern similar to the one of nonchagasic children. Although they were not statistically significant, TNF-α, IL-6, and sCD4 showed a tendency to reach high levels in the acutely infected group, whereas IL-2, IL-8, and IL-12 did not reveal changes with respect to the noninfected children. In summary, we report here the patterns of cytokines and soluble receptors in in the sera of children infected with Trypanosoma cruzi; we found significantly increased levels of sIL-2R and sCD8 in acute infection that decreased after therapy, and high levels of TNF-α, IL-6, and sCD4 in some of the acute patients. The measurement of sIL-2R and sCD8 may provide a useful tool in the follow-up of children with Chagas' disease.     

Serum soluble CD4 and CD8 levels in Kawasaki disease.

The levels of soluble CD4 (sCD4) and sCD8 in serum correlate with the T cell subset activation and may be important in monitoring and characterizing disease processes during immunological diseases. We compared acute Kawasaki disease (KD) with anaphylactoid purpura (AP) and acute febrile viral infections, such as measles and infectious mononucleosis (IM), in terms of serum sCD4 and sCD8 levels. The levels of serum sCD4 and sCD8 were measured by a sandwich enzyme immunoassay. In addition, peripheral blood mononuclear cell subsets were analysed by single and two-colour flow-cytometric analyses in KD and IM patients. The levels of serum sCD4 and sCD8 were significantly elevated in patients during acute stages of KD, measles and IM, but not AP. Peripheral blood CD4+, CD8+ and also HLA-DR+ T cells count did not increase during the acute stage of KD; however, peripheral blood CD8+ and HLA-DR+ T cell counts were increased during the acute stage of IM. Our results suggest that there is a low level of activation of peripheral blood T cells during acute KD, or that infiltrated T cells in some local tissues of KD patients contribute to the elevated levels of serum sCD4 and sCD8.     

Association of CD28 IVS3 +17T/C polymorphism with soluble CD28 in rheumatoid arthritis

Objective: Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology in which inflammatory pathology involves T cell activation and the CD28 costimulatory molecule involved in T cell presentation. The gene includes the CD28 IVS3 +17T/C polymorphism that could be associated with susceptibility to RA whereas the soluble concentrations of CD28 (sCD28) could be related to clinical activity. Methods: We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients. Methods: We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients. Results: RA patients had significantly higher frequencies of the CD28 T allele compared to HS (p = 0.032 OR = 1.59, C.I. 1.02–2.49). In addition, the IVS3 +17 T/T genotype frequency was also increased in RA vs. HS (p = 0.026). The RA patients showed higher sCD28 serum levels than HS (p = 0.001). Carriers of the T/T genotype in RA patients showed higher sCD28 levels than C/C carriers (p = 0.047). In addition, a correlation between sCD28 and Spanish HAQ-DI (correlation, 0.272; p = 0.016), was found. Conclusion: The T allele in CD28 IVS3 +17T/C polymorphism is associated with a susceptibility to RA in Western Mexico. In addition, increased sCD28 levels are related to T/T genotype in RA patients.