Comparison of plasma and urinary phytoestrogens in Japanese and Finnish women by time-resolved fluoroimmunoassay

Time-resolved fluoroimmunoassays (TR-FIA), with europium labeled phytoestrogens as tracers, were developed for the quantitative measurement of genistein, daidzein and enterolactone in plasma and urine for the purpose of screening large populations and studies on possible correlation between the values in biological fluids and the risk of western diseases. The mean values of the three phytoestrogens in plasma as determined by TR-FIA were similar to those obtained by gas chromatography-mass spectrometry (GC-MS). The urinary excretion levels of total individual phytoestrogens were higher than those obtained by GC-MS, with the exception of the daidzein values. However, comparing the assay results obtained by the present method and those obtained by GC-MS, a strong correlation was evident (r = 0.87 - 0.99, p < 0.001). We measured plasma levels of genistein, daidzein and enterolactone in 111 healthy Japanese women The mean and median levels of genistein were 406.8 and 306.3 nmol/l, respectively, and those of daidzein were 118.4 and 76.8 nmol/l, respectively. These levels are higher than those reported for Americans and Western Europeans. Isoflavone intake as calculated from dietary records (genistein: mean, 86.5 mircomol/day and daidzein: mean, 57.4 micromol/day) was correlated with the plasma concentrations observed (genistein: r = 0.287, p < 0.01 and daidzein: r = 0.313, p < 0.01). Plasma enterolactone levels were low in Japanese women (mean, about 10 nmol/l). The levels of urinary excretions of genistein, daidzein were also measured and it was found that, in the majority, the levels ranged between 5-25 and 5-50 micromol/24 h, respectively. In contrast, healthy Finnish women showed very low values of isoflavones (below 10 nmol/l in plasma (n = 87) and below 0.6 micromol/24 h in urine (n = 126) for both compounds) and high levels of enterolactone in both plasma and urine (plasma: mean, 25 nmol/l and urine: majority range, 1-7 micromol/24 h).     

Immediate effects of the serotonin antagonist granisetron on temporomandibular joint pain in patients with systemic inflammatory disorders

The aim of this study was to investigate if the 5-HT3 antagonist granisetron reduces temporomandibular joint (TMJ) pain in patients with systemic inflammatory joint disorders. Sixteen patients with systemic inflammatory joint disease with pain localized over the TMJ region and tenderness to digital palpation of the TMJ were included. The current resting pain (VASRest) and the pain during maximum mouth opening (VAS(MVM)) of the TMJs were assessed with a 100 mm visual analogue scale. An electronic pressure algometer was used to estimate the pressure pain threshold (PPT) over the lateral aspect of the TMJ. Venous blood was collected for measurement of the plasma and serum levels of 5-HT, erythrocyte sedimentation rate, rheumatoid factor and C-reactive protein. The selective 5-HT3 receptor antagonist granisetron or saline were injected into the posterior part of the upper TMJ compartment in a randomized double-blind manner. The patients in the granisetron group had lower VASRest than the patients in the saline group after 10 min. In the granisetron group, VASRest was decreased after 10 min, while VAS(MVM) was decreased and PPT increased after 20 min. In the saline group, VAS(MVM) was decreased after 20 min. In conclusion, granisetron has an immediate, short-lasting and specific pain reducing effect in TMJ inflammatory arthritis. The 5-HT3 receptor may therefore be involved in the mediation of TMJ pain in systemic inflammatory joint disorders.     

Serotonergic mechanisms influence the response to glucocorticoid treatment in TMJ arthritis

The aims of this study were to investigate the influence of serotonin (5-HT) on the effects of intra-articular injections of glucocorticoid on pain of the temporomandibular joint (TMJ) in patients with inflammatory disorders of the TMJ. The pretreatment synovial fluid 5-HT was negatively, and plasma 5-HT positively, correlated to change in TMJ pain after treatment. The pretreatment plasma 5-HT was positively correlated to change in pressure-pain threshold after treatment. In conclusion, this study shows that local and systemic serotonergic mechanisms partly determine the effect of intra-articular glucocorticoid treatment on TMJ pain in patients with chronic TMJ arthritis of systemic nature, while change in pressure-pain threshold over the TMJ is influenced by systemic serotonergic mechanisms.     

Diagnostic utility of anti-cyclic citrullinated peptide and anti-modified citrullinated vimentin antibodies in rheumatoid arthritis

Several autoantibodies found in RA are directed to epitopes in citrullinated proteins. One of them is anti modified citrullinated vimentin (Anti-MCV). We tested the value a newly developed ELISA for the detection of antibodies against a genetically modified citrullinated vimentin (anti-MCV) in comparison with an anti-CCP based ELISA system for the diagnosis of RA. Thirty-five patients with RA (mean age; 42.6 +/- 10.87 years, mean disease duration; 9.37 +/- 3.98 years) were enrolled in this study. Twenty -five ankylosing spondylitis (mean age; 35.88 +/- 6.64 years, mean disease duration; 10.25 +/- 4.61 years), and 19 healthy subjects (mean age; 40.26 +/- 5.11 years) served as controls. Anti-CCP antibodies and Anti-MCV antibodies were measured using ELISA. In all RA patients, mean anti- CCP level was 69.07 +/- 90.43 U/ml and anti-MCV level was 665.77 +/- 1040.19 U/ml. In patients with AS, the mean anti-CCP level was 10.7 +/- 5.22 U/ml and anti-MCV level was 40.54 +/- 20.15 U/ml. In healthy controls, the mean anti-CCP level was 11.11 +/- 7.65 U/ml, anti-MCV level was 23.12 +/- 12.04 U/ml. In patients with active RA, the mean serum anti-CCP level was 100.54 +/- 98.07 U/ml and anti-MCV level was 998.74 +/- 1154.93 U/ml. In patients with inactive RA, the mean serum anti-CCP level was 8.77 +/- 1.55 U/ml and anti-MCV level was 27.59 +/- 23.10 U/ml. According to these results; In patients with RA, the mean serum anti-MCV and anti-CCP levels were significantly high compared to patients with AS and healthy controls (p=0.002, p=0.001, p=0.002, p=0.001 respectively). The mean serum anti-MCV and anti- CCP levels were significantly higher in active patients with RA than in inactive patients with RA patients (p=0.001 and p=0.001 respectively). In inactive patients with RA, the mean serum anti-MCV and anti-CCP levels were similar in patients with AS and patients (p=0.484, p=0.308, p=0.09 and p=0.222 respectively). The mean serum anti-MCV levels were correlated with DAS 28 (r=0.531, p=0.001), VAS score (r=0.332, p=0.01), ESR (r=0.458, p=0.001), serum CRP levels (r=0.568, p=0.01), serum RF levels (r=0.529, p=0.001), swollen joints number (r=0.525, p=0.001) and tender joints number (r=0.638, p=0.001). As a result; measurement of serum anti-MCV levels is useful for diagnosis of RA and combined use of anti-MCV and RF may be more useful prognostic factor than either method alone, RF and anti-CCP.     

Influence of serotonin on the analgesic effect of granisetron on temporomandibular joint arthritis

The influence of circulating serotonin (5-HT) on the effects of intra-articular administration of granisetron on temporomandibular joint (TMJ) pain was investigated in 11 patients with chronic polyarthritides. An analgesic effect superior to placebo has been shown previously. The change in TMJ movement pain intensity was negatively correlated to circulating 5-HT; that is, the higher the 5-HT before injection, the greater the reduction of pain intensity. The resting pain intensity reduction was not related to 5-HT. In conclusion, this study indicates a stronger short-term analgesic effect on TMJ movement pain by intra-articular administration of the 5-HT3 receptor antagonist granisetron in patients with high levels of circulating 5-HT.     

Serum E-selectin and erythrocyte membrane Na+K+ ATPase levels in patients with rheumatoid arthritis

We conducted this study to assess serum soluble E-selectin (sE-selectin) levels and erythrocyte membrane Na(+)K(+) ATPase activity in patients with rheumatoid arthritis (RA) and correlate the levels with disease activity. Levels of sE-selectin were measured in the serum of 20 patients with RA and 20 control subjects by an enzyme-linked immunosorbant assay. Na(+)K(+) ATPase activity was determined by a colorimetric method in RA patients and healthy controls. There were no statistically significant differences between the two groups with respect to demographic data such as age and sex (p > 0.05). The serum levels of sE-selectin, ESR and C-reactive protein (CRP) in RA patients were significantly higher than in healthy controls (p < 0.001). Erythrocyte membrane Na(+)K(+) ATPase activity was significantly lower in the RA group than in the control group (p < 0.001). Correlation analysis revealed significant positive correlations between soluble E-selectin and ESR (r = 0.457; p < 0.05) and CRP (r = 0.682; p < 0.01) levels. There were statistically significant negative correlations between erythrocyte membrane Na(+)K(+) ATPase activity and ESR (r = -0.450; p < 0.05) and CRP (r = -0.446; p < 0.05) levels. Additionally, a significant negative correlations between sE-selectin and Na(+)K(+) ATPase activity was observed (r = -0.80; p < 0.001). These results show that decreases in erythrocyte membrane Na(+)K(+) ATPase activity and increases in sE-selectin are observed in RA, and that increased levels of sE-selectin may also reflect disease status or activity.     

类风湿关节炎患者血清维生素D水平与疾病活动度相关

目的:探讨类风湿关节炎(Rheumatoid arthritis,RA)患者血清维生素D(25(OH)D)水平与疾病活动度的关系。方法:总共纳入180例RA患者,同时纳入60例年龄、性别相匹配的健康对照。检测所有参与者的血清25(OH)D水平及所有RA患者C反应蛋白和血沉。同时获取RA患者晨僵时间、疼痛视觉模拟表评分、乏力视觉模拟表评分、压痛关节数、肿胀关节数、健康评估量表得分、情绪变化量表得分等。利用RA患者28个关节疾病活动评分(Disease activity score in 28 joints,DAS28)评估RA疾病活动度。结果:相对于健康对照组(43.89±16.28 ng/m L),RA患者的血清25(OH)D明显降低(28.52±8.95 ng/m L)(P=0.000)。RA患者的血清25(OH)D水平越低,压痛关节数、肿胀关节数越多(P=0.043,r=-0.132;P=0.017,r=-0.177),血沉、C反应蛋白越高(P=0.018,r=-0.177;P=0.007,r=-0.200),同时DAS28评分越高(P=0.007,r=-0.201);患者的晨僵时间、疼痛评分、乏力评分、健康评估量表得分及情绪量表得分与血清维生素D水平负相关(P=0.043,r=-0.151;P=0.019,r=-0.175;P=0.006,r=-0.205;P=0.048,r=-0.147;P=0.017,r=-0.178)。结论:RA患者血清维生素D普遍缺乏,并且与RA患者疾病活动度负相关。     

便秘型肠易激综合征患者血清神经肽Y、P物质和5-羟色胺水平与焦虑抑郁的相关性

为探讨便秘型肠易激综合征(constipation-predominant irritable bowel syndrome, C-IBS)患者血清神经肽Y (neuropeptide Y, NPY)、P物质(substance P, SP)以及5-羟色胺(5-hydroxytryptamine, 5-HT)水平与焦虑抑郁的相关性,本研究选取确诊为C-IBS的患者35例,健康对照组35例,采用焦虑自评表(self-rating anxiety scale, SAS)和抑郁自评表(self-rating depression scale, SDS)评定C-IBS患者和健康对照组的焦虑和抑郁状况。酶联免疫吸附法(enzyme-linked immunosorbent assay, ELISA)检测C-IBS患者和健康对照组血清NPY、SP以及5-羟色胺含量变化。结果表明,IBS-C中出现抑郁、焦虑或者无抑郁、焦虑的患者在各方面(性别,年龄以及病程)无统计学意义。与健康对照组相比,C-IBS组NPY和SP水平显著降低(t=7.96, p<0.01; t=5.63, p<0.01),5-HT则表现出显著性升高(t=8.06, p<0.001)。C-IBS组SAS和SDS评分结果与健康对照组相比有着显著性的升高(t=12.13, p<0.001; t=11.34, p<0.001)。C-IBS患者血清NPY与SAS和SDS评分均呈负相关(r=-0.62, p<0.001; r=-0.69, p<0.001)。C-IBS患者血清SP水平与SAS和SDS评分均呈负相关(r=-0.63, p<0.001; r=-0.57, p<0.001)。C-IBS患者血清5-HT与SAS和SDS评分均呈正相关(r=0.74, p<0.001; r=0.68, p<0.001)。本研究初步表明,C-IBS患者血清中NPY和SP水平降低,并与焦虑、抑郁评分呈负相关性,5-HT在C-IBS患者血清中升高,与焦虑、抑郁评分呈正相关性,NPY、SP以及5-HT可能在便秘型肠易激综合征出现焦虑、抑郁的过程中发挥重要作用。     

Gelsolin蛋白在类风湿性关节炎和系统性红斑狼疮的临床诊断及疾病活动度评价中的意义

目的:分析gelsolin蛋白对类风湿性关节炎(rheumatoid arthritis,RA)和系统性红斑狼疮(systemic lupus erythematosus,SLE)的临床诊断及疾病活动度评价的意义。方法:采集RA 30名和SLE 47名及健康人群50名的临床资料及血清标本,定量Western Blot法检测血清gelsolin水平。分析gelsolin蛋白与RA和SLE患者临床表现及疾病活动度的相关性。结果:RA、SLE和正常对照组之间性别、年龄、血红蛋白、血小板、血红细胞、血白细胞之间没有显著差异;RA患者出现CRP、转氨酶、RF、CCP异常的阳性率明显高于SLE患者(P0.05);而SLE患者出现白蛋白、尿蛋白、尿红细胞、尿素氮、ANA、肌酐异常增高的几率高于RA患者(P0.05)。gelsolin蛋白在SLE和RA血清中的含量均显著低于正常人(P0.05),且RA患者含量更低(P0.05)。gelsolin蛋白滴度与RA的疾病活动度无明显相关性(r=0.089,P=0.652),而与SLE的疾病活动度呈显著负相关(r=0.646,P0.05)。gelsolin蛋白正常组RA患者的转氨酶升高、CRP、RF、CCP阳性率均显著高于SLE患者(P0.05)。gelsolin蛋白降低组SLE患者的白蛋白、尿蛋白、尿红细胞、尿素氮、ANA、肌酐阳性率显著高于RA患者(P0.05)。结论:gelsolin蛋白滴度检测可作为RA和SLE临床辅助诊断手段,其滴度变化可作为SLE疾病活动度进展的预判指标。     

15-Keto-13,14-dihydroprostaglandin E2- and F2 alpha-metabolite levels in blood from men and women given prostaglandin E2 orally

Prostaglandin E2 (PGE2) was administered orally in a dose of 1 mg to healthy males (n = 20) and females (n = 10). Blood levels of 15-keto-13,14-dihydroprostaglandin F2 alpha (PGF2 alpha-M) and 15-keto-13,14-dihydroprostaglandin E2 (PGE2-M), determined as the rearrangement product 11-deoxy-15-keto-13,14-dihydro-11 beta, 16-cycloprostaglandin E2 (PGE2-cyclo-M), were measured. The levels of the two PG metabolites increased already 10 minutes after ingestion of the tablet and the mean peak value for PGE2-cyclo-M in the men was 4.64 nmol/l which was reached 50 minutes after PGE2 administration. The mean peak value in women was 4.99 nmol/l which was obtained after 30 minutes. The increase in PGE2-cyclo-M concentration was significantly faster (p less than 0.05) in women than in the men. The mean plasma concentration of PGF2 alpha in males were 0.20 nmol/l prior to treatment and rose after PGE2 ingestion to mean peak level of 0.84 nmol/l after 70 minutes. The corresponding values for the females were 0.18 nmol/l and 0.88 nmol/l 50 minutes into treatment. When the data from both sexes were amalgamated PGE2-cyclo-M peak levels were reached significantly (p = 0.004) sooner than the PGF2 alpha-M peak. The two PG metabolites returned to baseline levels in 70% of the individuals after 240 minutes. The increase in PGF2 alpha-M concentration following oral administration of PGE2 indicates that part of the PGE2 was reduced to PGF2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum thymidine activity and somatomedin-C levels in children and adolescents with Turner's syndrome: effect of chronic estrogen and progestogen replacement therapy

Turner's syndrome has been used as a model of primary hypogonadism to assess the role of estrogen-progestogen replacement therapy on serum thymidine activity (TA) and somatomedin-C (Sm-C) levels. 33 subjects with gonadal dysgenesis were studied: 10 untreated and 13 treated with estrogen-progestogen combination. In 10 untreated patients serum TA was 1.02 +/- (SEM) 0.04 U/ml and serum Sm-C value was 27.82 +/- 4.14 nmol/l, both similar to those in the age-matched normal children. A positive correlation was found between Sm-C and the bone age (r = 0.891, p less than 0.002). In the 13 treated subjects, the estrogen-progestogen combination as replacement therapy induced a significant increase in Sm-C level (40.52 +/- 4.30 nmol/l, p less than 0.05). No variation was observed for serum thymidine activity between the two groups of subjects.     

Serum paraoxonase activity decreases in rheumatoid arthritis

OBJECTIVE: To estimate the alterations of paraoxonase 1 (PON1) and high-density lipoprotein (HDL) in rheumatoid arthritis (RA). DESIGN AND METHODS: We investigated the serum enzyme activity and concentration of PON1 and their relationship with serum lipids, high-density lipoprotein (HDL) parameters, and acute phase reactants of serum amyloid A (SAA) and C-reactive protein (CRP) in patients with RA. RESULTS: Serum paraoxonase (PON) activity was significantly decreased in RA patients (n = 64, 131 +/- 53 micro mol/min/L) compared with healthy subjects (n = 155, 164 +/- 59) despite the absence of any difference in serum lipid levels between the two groups. This decrease of serum PON activity in RA patients was found in every genotype (Q/Q, Q/R, R/R) of PON1 at 192 Q/R. There was a different distribution in PON1 Q/R genotypes between RA patients and healthy subjects, and RA patients exhibited less (44%) positive PON1-Q than did the healthy subjects (66%). In a further investigation of age- and gender-matched subgroups of RA (n = 25) and healthy subjects (n = 25), not only serum PON activity, but also lecithin-cholesterol acyltransferase (LCAT) was found to be significantly decreased in RA patients (125 +/- 61 micro mol/min/L, 63.2 +/- 17.2 nmol/ml/hr/37 degrees C) than in healthy subjects (169 +/- 67, 74.7 +/- 19.5), respectively. PON1 and LCAT as well as HDL constituent apolipoprotein (apo) AI and apo AII, were altered significantly in RA patients. CONCLUSIONS: Acute-phase HDL, which is remodeled structurally and functionally in RA, might be less anti-atherogenic due to the impairment of original HDL function. These alterations of HDL in RA patients may explain in part the reported increase in cardiovascular mortality in patients with RA.     

p53 serum antibodies as prognostic indicator in head and neck cancer

p53 antibodies are a new serological parameter of unknown potential in patients with malignancies. Their occurrence has been described in various types of cancer patients. The mechanism underlying the immunization process is still unclear. We investigated the incidence of p53 serum antibodies in 143 head and neck cancer patients with an enzyme-linked immunosorbent assay. The post-therapy course of two matched study groups (n = 38 each), one p53-antibody-seropositive and one p53-antibody-seronegative, was followed up for 24 months. Thirty-nine head and neck cancer patients (27.3%) were seropositive for p53 antibodies. During the follow-up, the p53-antibody-seropositive patients accounted for more local tumor recurrences (n = 12 versus n = 8) and more tumor-related deaths (n = 11 versus n = 5) than did seronegative patients, and second primary tumors (n = 9 versus n = 0) occurred exclusively in seropositive patients. In total, therapy failures (recurrences, tumor-related deaths, second primaries) were observed in 17/38 cases (44.7%) in the p53-antibody-seropositive group and in 8/38 cases (21.1%) in the p53-antibody-seronegative group. These results, after a follow-up of 2 years, seem to indicate a prognostic value of p53 serum antibodies for therapy failure in patients with head and neck cancer. Received: 5 December 1996 / Accepted: 4 January 1997     

Genetic association of CCR5 promoter single nucleotide polymorphism in seronegative and seropositive rheumatoid arthritis

The aim of this study was to investigate the possible role of the CCR5 59029 A→G promoter point mutation polymorphism in determining the susceptibility to rheumatoid factor-positive and rheumatoid factor-negative rheumatoid arthritis. This polymorphism was assessed in 85 seropositive and 39 seronegative rheumatoid arthritis patients and in 126 healthy individuals of the same geographic and ethnic origin. We found an increase in the genetic frequency of the A allele in the 59029 A→G promoter region of the CCR5 receptor in patients with rheumatoid arthritis compared with healthy controls (p = 0.01; OR = 1.5, 95% CI (1.0-2.2). Likewise, the homozygous state for the A allele was found to be more frequent in rheumatoid arthritis patients, again when compared with healthy controls (p = 0.03; OR = 1.8, 95% CI 1.0-3.0). The increased frequency of the A allele was more evident in the more benign, seronegative rheumatoid arthritis group when compared with controls (p = 0.003; OR 2.4 95% CI 1.3-4.4), and when combining the A homozygous and the AG heterozygous patients compared with healthy subjects. These results suggest that this CCR5 promoter polymorphism seems to play an important role in determining different clinical courses in both forms of rheumatoid arthritis.     

The major rheumatoid factor cross-reactive idiotype is dominantly expressed by Staphylococcus aureus Cowan strain I-activated CD5+ control B cells.

Some seropositive (RF+) and seronegative (RF-) rheumatoid arthritis (RA) patients selectively express high concentrations of the major RF cross-reactive idiotype (RCRI) in their sera and generate high frequencies of RCRI+ pokeweed mitogen (PWM)-induced plasma cells from their peripheral blood mononuclear cells (PBM). To determine if normal individuals can express RCRI in vitro, B cells from controls were activated with Staphylococcus aureus Cowan strain I (SAC) bacteria to identify RCRI and RF production. In addition, we studied the relationship of RCRI expression with the subset of B cells bearing CD5. Control CD5+ B cells are responsible for RCRI expression following SAC activation. We also observed that RCRI is dominantly expressed by control SAC-induced B cells in frequencies comparable to that expressed by some RA and juvenile rheumatoid arthritis patients' PBM activated by PWM. Therefore, the frequency of RCRI+ B cells in control and arthritis patients' PBL may be similar, or the selection and/or regulation of RCRI+ B-cell expression in vitro and in vivo may be different in arthritis patients compared to normal individuals.     

Sera from HTLV-III/LAV antibody-positive individuals mediate antibody-dependent cellular cytotoxicity against HTLV-III/LAV-infected T cells

The causative agent of the acquired immunodeficiency syndrome (AIDS) has been shown to be a human retrovirus called human T lymphotropic virus (HTLV)-III or lymphadenopathy-associated virus (LAV). The nature of the protective immune response against this virus is currently unknown. We report here results using an antibody-dependent cellular cytotoxicity (ADCC) assay which has been developed for measuring a specific immune response against HTLV-III/LAV. Forty-four sera were examined for their ability to mediate ADCC against HTLV-III/LAV-infected T cells. Sera from healthy HTLV-III/LAV seropositive individuals in the presence of mononuclear cells from healthy HTLV-III/LAV seronegative donors exhibited significantly higher levels of ADCC activity compared to sera from patients with AIDS. Western blot analysis of serum samples indicated that antibody reactivity with the p24 protein of HTLV-III/LAV correlated with higher levels of ADCC activity than did reactivity with Gp120/160. The observation that sera from healthy HTLV-III/LAV seropositive individuals mediated higher levels of ADCC activity than did sera obtained from subjects with AIDS suggests that ADCC may represent a protective immune response to infection with HTLV-III/LAV.     

Lack of autoantibody production associated with cytomegalovirus infection

To confirm an association between cytomegalovirus (CMV) infection and the presence of antibodies to Smith (Sm), to ribonucleoprotein (RNP), and to a component of the U1 ribonucleoproteins (U1-70 kD), we measured antibodies to these protein antigens using an enzyme immunoassay and an immunoblot. The antibodies were measured in the sera of 80 healthy subjects, one-half of whom were naturally CMV seropositive and one-half were CMV seronegative, and in eight subjects immunized with a live attenuated strain of CMV. None of the vaccinees developed antibodies to Sm, to RNP, or to U1-70 kD at either 4 or 12 months after immunization. Additionally, there was no statistically significant association between levels of antibodies to Sm or to RNP and between sera obtained from vaccinees, natural CMV seropositive individuals, and CMV seronegative individuals. One CMV seropositive serum and one CMV seronegative serum tested positive for antibodies to U1-70 kD. These data indicate that neither wild-type infection nor the live-attenuated Towne vaccine frequently induce autoantibody production.     

Soluble IL-2 receptor levels in serum from blood donors seropositive for HIV

Serum levels of soluble IL-2R (sIL-2R) were measured in blood donors seropositive for HIV. Approximately one-half (53/101) of these seropositive donors exhibited increased serum sIL-2R levels compared with seronegative controls (n = 65). Further, a significant inverse correlation was observed between serum sIL-2R levels and CD4 cell levels in seropositive study participants. These findings suggest that increased serum sIL-2R levels in HIV infection may be linked to CD4 cell loss, and thus reflective of the stage of HIV-induced disease.     

Immunodominant "asymptomatic" herpes simplex virus 1 and 2 protein antigens identified by probing whole-ORFome microarrays with serum antibodies from seropositive asymptomatic versus symptomatic individuals

Herpes simplex virus 1 (HSV-1) and HSV-2 are medically significant pathogens. The development of an effective HSV vaccine remains a global public health priority. HSV-1 and HSV-2 immunodominant "asymptomatic" antigens (ID-A-Ags), which are strongly recognized by B and T cells from seropositive healthy asymptomatic individuals, may be critical to be included in an effective immunotherapeutic HSV vaccine. In contrast, immunodominant "symptomatic" antigens (ID-S-Ags) may exacerbate herpetic disease and therefore must be excluded from any HSV vaccine. In the present study, proteome microarrays of 88 HSV-1 and 84 HSV-2 open reading frames(ORFs) (ORFomes) were constructed and probed with sera from 32 HSV-1-, 6 HSV-2-, and 5 HSV-1/HSV-2-seropositive individuals and 47 seronegative healthy individuals (negative controls). The proteins detected in both HSV-1 and HSV-2 proteome microarrays were further classified according to their recognition by sera from HSV-seropositive clinically defined symptomatic (n = 10) and asymptomatic (n = 10) individuals. We found that (i) serum antibodies recognized an average of 6 ORFs per seropositive individual; (ii) the antibody responses to HSV antigens were diverse among HSV-1- and HSV-2-seropositive individuals; (iii) panels of 21 and 30 immunodominant antigens (ID-Ags) were identified from the HSV-1 and HSV-2 ORFomes, respectively, as being highly and frequently recognized by serum antibodies from seropositive individuals; and (iv) interestingly, four HSV-1 and HSV-2 cross-reactive asymptomatic ID-A-Ags, US4, US11, UL30, and UL42, were strongly and frequently recognized by sera from 10 of 10 asymptomatic patients but not by sera from 10 of 10 symptomatic patients (P < 0.001). In contrast, sera from symptomatic patients preferentially recognized the US10 ID-S-Ag (P < 0.001). We have identified previously unreported immunodominant HSV antigens, among which were 4 ID-A-Ags and 1 ID-S-Ag. These newly identified ID-A-Ags could lead to the development of an efficient "asymptomatic" vaccine against ocular, orofacial, and genital herpes.     

Could the expression of CD86 and FcγRIIB on B cells be functionally related and involved in driving rheumatoid arthritis?

Aberrant immune responses play a pivotal role in the processes that cause inflammation and joint damage in patients with rheumatoid arthritis (RA). Polyclonal B cell activation and the production of autoantibodies are immunological hallmarks of the disease. However, controversy surrounds the pathogenicity of autoantibodies, mainly because not all patients are seropositive (10% of RA patients are seronegative), suggesting that they could be markers rather than makers of disease. Catalán and collaborators report that patients with RA display reduced expression of FcγRIIB on memory B cells and plasma cells, which inversely correlates with autoantibody levels. Considering that FcγRIIB stimulation down-regulates antibody production, this work strengthens the link between autoantibodies and pathogenicity.