Prevalence and molecular identification of Trichinella species isolated from wildlife originating from Limpopo and Mpumalanga provinces of South Africa.

Trichinella species are widely distributed on all continents with the exception of Antarctica, although the full spectrum of Trichinella species found in sub-Saharan African countries, and their hosts, has not been fully documented. This study was conducted to determine the prevalence of Trichinella in wildlife from the Greater Kruger National Park (GKNP) and adjacent areas located in the Limpopo and Mpumalanga provinces of South Africa, and to identify the species and/or genotypes of Trichinella larvae isolated from muscle tissues, using molecular techniques. A review of Trichinella spp. and their wildlife hosts reported during 1964-2011 was also conducted and the results were compared with our current study. Ninety samples representing 15 mammalian, two bird and three reptile species were screened for Trichinella infection during 2012-2016, using artificial digestion. Isolates detected were identified using a multiplex polymerase chain reaction (PCR) amplification of the internal transcriber spacers ITS1 and ITS2, and expansion segment V (ESV) regions of ribosomal DNA, followed by molecular analysis of the sequences. Twenty samples from seven wildlife species were positive for Trichinella spp. larvae, with an overall prevalence of 21.1% (20/90). The prevalence was higher in carnivores (18.9%, 18/90) than in omnivores (2.2%, 2/90). Analysis of sequences showed that eight of the isolates - two from spotted hyaena (Crocuta crocuta) (2/8), three from lion (Panthera leo) (3/13), one from leopard (Panthera pardus) (1/6), one from small spotted genet (Genetta genetta) (1/2) and one Nile monitor lizard (Varanus niloticus) (1/2) - conformed to Trichinella zimbabwensis. One isolate from a hyaena was grouped under the encapsulated species clade comprising T. nelsoni and genotype Trichinella T8 reported to be present in South Africa. This is the first report confirming natural infection by T. zimbabwensis in hyaena, leopard, genet and Nile monitor lizard, adding to the body of knowledge on the epidemiology of Trichinella infections in the Greater Kruger National Park of South Africa. Ten Trichinella-like larval isolates recovered after digestion from four wildlife species in this study (2012-2016) revealed inconclusive results due to DNA degradation resulting from poor storage or too few larvae for analysis, in comparison to 20 unidentified isolates from five wildlife species during the 1964-2011 period.

l-Lysine Acts as a Serotonin Type 4 Receptor Antagonist to Counteract In Vitro and In Vivo the Stimulatory Effect of Serotonergic Agents on Aldosterone Secretion in Man.

In the normal human adrenal gland, serotonin (5-HT) stimulates aldosterone secretion through the 5-HT4 receptor (5-HT4R). However, the physiological role of the serotonergic control of adrenocortical function is not known. In the present study, we have investigated the ability of l-Lysine, which has been shown to act as a 5-HT4 receptor antagonist, to counteract in vitro and in vivo the stimulatory effect of 5-HT4R agonists on aldosterone production. l-Lysine was found to inhibit aldosterone production induced by 5-HT and the 5-HT4R agonists BIMU8 from cultured human adrenocortical cells. The action of l-Lysine (4.95 g/day orally) on the adrenal cortex was also evaluated in 20 healthy volunteers in a double blind, cross-over, placebo controlled study. l-Lysine had no significant influence on basal plasma aldosterone levels and the aldosterone responses to upright posture, tetracosactide, and low sodium diet (10 mmol/day for 3 days). Conversely, l-Lysine significantly reduced the surge of plasma aldosterone induced by metoclopramide indicating that l-Lysine is able to efficiently antagonize the adrenal 5-HT4 receptors in vivo. These results suggest that l-Lysine supplementation may represent a new treatment of primary adrenal diseases in which corticosteroid hypersecretion is driven by overexpressed 5-HT4 receptors.

IL-1beta mediates MMP secretion and IL-1beta neosynthesis via upregulation of p22(phox) and NOX4 activity in human articular chondrocytes.

OBJECTIVES: Osteoarthritis (OA) is characterized by a progressive alteration of the biochemical properties of the articular cartilage. Inflammation plays a major role in OA, particularly through the cytokine Interleukine-1ß, promoting reactive oxygen species (ROS) generation and matrix metalloproteinases (MMP) synthesis by the chondrocytes, orchestrating matrix proteolysis. NADPH oxidases (NOX) are membrane enzymes dedicated to the production of ROS. Role of oxidative stress is well established in OA; however, contribution of NOX in this process is still poorly documented. In this study, we addressed the role of NOX in primary human articular chondrocytes (HAC) upon inflammatory conditions--namely IL-1ß and OA. DESIGN: HAC were collected from patients undergoing hip surgery. Chondrocytes were treated with IL-1ß and NOX inhibitors Diphenylene Iodonium, GKT136901, Tiron and Heme oxygenase-1 before MMP expression and NOX activity assessment. Finally, NOX4 expression was compared between OA and non OA parts of hip cartilage (n = 14). RESULTS: This study establishes for the first time in human that NOX4 is the main NOX isoform expressed in chondrocytes. We found a significant upregulation of NOX4 mRNA in OA chondrocytes. Expression of NOX4/p22(phox) as well as ROS production is enhanced by IL-1ß. On the other hand, the use of NOX4 inhibitors decreased IL-1ß-induced collagenase synthesis by chondrocytes. Moreover, our study support the existence of a redox dependant loop sustaining pro-catabolic pathways induced by IL-1ß. CONCLUSIONS: This study points out NOX4 as a new putative target in OA and suggests that NOX-targeted therapies could be of interest for the causal treatment of the pathology.

[First junior doctors: State of play one year after the implementation of the consolidation phase within the diploma of specialized studies in internal medicine and clinical immunology]. / Premiers docteurs juniors : état des lieux à un an de la mise en place de la phase de consolidation au sein du diplôme d'études spécialisées de médecine interne et immunologie clinique.

INTRODUCTION: The 2017 reform of the 3rd cycle of medical studies introduced the concept of supervised autonomy with the creation of a new junior doctor (JD) status. The aim of this work was to interview the first class of JDs in internal medicine and clinical immunology (IMCI) regarding the progress and implementation of this final year of internship. METHODS: The IMCI JDs were invited to complete an anonymous online survey, contacted by email and social networks. RESULTS: The questionnaire received 36 responses out of an estimated fifty JDs. The majority of JDs spent more than 70% of their time on conventional hospitalisation and less than 20% on scheduled hospitalisation. Most of them would have preferred to do more consultations and provide expert counsels. Weekly working hours were not respected for the majority of JDs. Personal education and academic formation were not respected for 77.8% of JDs. Overall, 75% were satisfied with their empowerment and 88.6% felt that the transition to post residency would be easier with the consolidation phase. A third reported that their residency had confirmed their apprehension about practising as an internist, and even that this apprehension might call into question their future practice. CONCLUSION: This survey is an initial assessment of the implementation of the JD year in the IMCI residency. A collective effort around this last year of internship seems to be essential to ensure the personal and professional development of young internists.

The occurrence of Trichinella zimbabwensis in naturally infected wild crocodiles (Crocodylus niloticus) from the Kruger National Park, South Africa.

Trichinella zimbabwensis has been found naturally infecting crocodiles (Crocodylus niloticus) in Zimbabwe, Mozambique, Ethiopia and South Africa, as well as monitor lizards (Varanus niloticus) in Zimbabwe. The reports on natural infections were mostly accidental rather than structured surveys and involved very few animals. Previous surveillance studies in South Africa reported a 38.5% prevalence of T. zimbabwensis among wild crocodiles tested from the Mpumalanga province and Kruger National Park (KNP). No studies have been conducted to date on the geographical distribution and occurrence of T. zimbabwensis in wild crocodiles and varans in countries in southern Africa. Recent outbreaks of pansteatitis in crocodile populations of the KNP, South Africa, provided an opportunity to conduct a more structured survey aimed at elucidating the occurrence and distribution of T. zimbabwensis in culled wild crocodile populations within the KNP. Results from this study showed that T. zimbabwensis occurred in 10 out of 12 culled crocodiles form the KNP. The results also showed that the natural distribution of T. zimbabwensis in crocodiles includes all the major river systems in the KNP. The predilection sites of larvae in muscles followed a different pattern in naturally infected crocodiles compared to observations in experimentally infected mammalian hosts.

Efficacy of self-management program associated with a spa therapy for knee osteoarthritis patients (GETT 2): a research protocol for a randomized trial.

INTRODUCTION: Osteoarthritis is a chronic pathology that involves multidisciplinary management. Self-management for patients is an essential element, present in all international guidelines. During the time of the spa therapy, the patient is receptive to take the advantage of self-management workshops. The aim of this study is to assess the effects of 18 days spa therapy associated with a self-management intervention in patients with knee osteoarthritis in comparison with spa therapy alone on a priority objective, personalized and determined with the patient, chosen in the list of 5 objectives determined during the self-management initial assessment. METHODS AND ANALYSIS: Two hundred fifty participants with knee osteoarthritis will participate to this multicenter, prospective, randomized, controlled study. All patients will benefit 18 days of spa therapy and patients randomized in the intervention group will participate to 6 self-management workshops. Randomization will be centralized. The allocation ratio will be 1:1. Data analysts and assessor will be blinded. The primary outcome is the effectiveness of the educational workshops associated with spa therapy in comparison with spa therapy alone on a priority objective, measured by Goal Attainment Scaling (GAS). The secondary outcomes are disability, health-related quality of life, and pain intensity. ETHICS AND DISSEMINATION: Ethics were approved by the CPP Sud-Méditerranée II. The results will be disseminated in a peer-reviewed journal and disseminated at PRM, rheumatology, and orthopedics conferences. The results will also be disseminated to patients. TRIAL REGISTRATION: Trial registration number NCT03550547. Registered 8 June 2018. Date and version identifier of the protocol. Version N°6 of March 12, 2018.

Intermediate ice scour disturbance is key to maintaining a peak in biodiversity within the shallows of the Western Antarctic Peninsula.

Climate-related disturbance regimes are changing rapidly with profound consequences for ecosystems. Disturbance is often perceived as detrimental to biodiversity; however, the literature is divided on how they influence each other. Disturbance events in nature are diverse, occurring across numerous interacting trophic levels and multiple spatial and temporal scales, leading to divergence between empirical and theoretical studies. The shallow Antarctic seafloor has one of the largest disturbance gradients on earth, due to iceberg scouring. Scour rates are changing rapidly along the Western Antarctic Peninsula because of climate change and with further changes predicted, the Antarctic benthos will likely undergo dramatic shifts in diversity. We investigated benthic macro and megafaunal richness across 10-100 m depth range, much of which, 40-100 m, has rarely been sampled. Macro and megafauna species richness peaked at 50-60 m depth, a depth dominated by a diverse range of sessile suspension feeders, with an intermediate level of iceberg disturbance. Our results show that a broad range of disturbance values are required to detect the predicted peak in biodiversity that is consistent with the Intermediate Disturbance Hypothesis, suggesting ice scour is key to maintaining high biodiversity in Antarctica's shallows.

Trichinella zimbabwensis in a naturally infected mammal.

Trichinella zimbabwensis has been detected in wild and farmed Nile crocodiles (Crocodylus niloticus) and in wild monitor lizards (Varanus niloticus) of several African countries, but it has never been detected in mammals in nature, in spite of its infectivity to rodents, pigs, foxes and monkeys under laboratory conditions. The aim of this work was to describe the first detection of T. zimbabwensis in a naturally infected lion (Panthera leo) of the Kruger National Park (KNP) of South Africa. The sequence of the expansion segment V, a highly variable non-coding sequence of the large subunit ribosomal RNA of the genus Trichinella, of larvae from the lion was identical to that of larvae of T. zimbabwensis collected from a Nile crocodile originating from the same locality as the lion, suggesting a possible transmission of this parasite between mammals and reptiles. The KNP proves to be a very interesting area for parasites of the genus Trichinella since three taxa (Trichinella nelsoni, Trichinella T8 and T. zimbabwensis) circulate among the wildlife of this protected area.

Apolipoprotein A-I and platelet factor 4 are biomarkers for infliximab response in rheumatoid arthritis.

OBJECTIVES: The use of biologicals such as infliximab has dramatically improved the treatment of rheumatoid arthritis (RA). However, factors predictive of therapeutic response need to be identified. A proteomic study was performed prior to infliximab therapy to identify a panel of candidate protein biomarkers of RA predictive of treatment response. METHODS: Plasma profiles of 60 patients with RA (28 non-responders (as defined by the American College of Rheumatology 20% improvement criteria (ACR20)) negative and 32 responders (ACR70 positive) to infliximab) were studied by surface enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS) technology on two types of arrays, an anion exchange array (SAX2) and a nickel affinity array (IMAC3-Ni). Biomarker characterisation was carried out using classical biochemical methods (purification by ammonium sulfate precipitation or metal affinity chromatography) and identification by matrix assisted laser desorption/ionisation time-of-flight (MALDI-TOF) MS analysis. RESULTS: Two distinct protein profiles were observed on both arrays and several proteins were differentially expressed in both patient populations. Five proteins at 3.86, 7.77, 7.97, 8.14 and 74.07 kDa were overexpressed in the non-responder group, whereas one at 28 kDa was increased in the responder population (sensitivity>56%, specificity>77.5%). Moreover, combination of several biomarkers improved the sensitivity and specificity of the detection of patient response to over 97%. The 28 kDa protein was characterised as apolipoprotein A-I and the 7.77 kDa biomarker was identified as platelet factor 4. CONCLUSIONS: Six plasma biomarkers are characterised, enabling the detection of patient response to infliximab with high sensitivity and specificity. Apolipoprotein A-1 was predictive of a good response to infliximab, whereas platelet factor 4 was associated with non-responders.

[Sonography versus electrodiagnosis for the diagnosis of carpal tunnel syndrome in routine practice]. / Comparaison de l'échographie et de l'électroneurographie pour le diagnostic du syndrome du canal carpien en pratique courante.

INTRODUCTION: Many studies had been performed in the last years to prove the usefulness of ultrasonographic measurements of the median nerve in the diagnosis of carpal tunnel syndrome (CTS). We wanted to determine its reliability and to compare this technology with electromyography (EMG) in ordinary diagnostic conditions. METHODS: The study involved 90 wrists with suspected CTS, 35 controlateral wrists and 52 control wrists. The diagnosis of CTS was confirmed in 81 cases by the hand symptom diagram and the Tinnel and Phalen sign. The EMG examination evaluated medianulnar sensory latency difference to the ring finger and wrist-to-palm sensory conduction velocity. For the ultrasound diagnosis, the cross sectional area of the median nerve at the level of the pisiform bone, was considered. The sensitivity and specificity of the two techniques was calculated. RESULTS: Sensitive electroneurographic parameters showed a sensibility and specificity respectively of 79 and 80%. The cut-off point for ultrasound sensibility and specificity using ROC analysis was 11mm(2) for mean cross-sectional area. Sensitivity and specificity found in this way were 72% and 56%. Reliability was good with intra- and inter-reader intraclass correlation coefficients of 0.99, and interobserver coefficient of 0.88. Sonography found seven CTS among the 17 clinical CTS with normal electrophysiological findings. A statistically correlation was found between the cross-sectional section and the sensitive electrophysiologic parameters (r=0.43, p<0.001). CONCLUSIONS: In our study, ultrasonographic diagnostic value are not as good as electrophysiological value, like found in recent literature, probably because of the composition of our group of patients which is including many causes of acroparesthesias. This can mean that in clinical practice, sonography is a complementary tool instead, for example in cases of equivocal EMG.

Reactive oxygen species and NADPH oxidase 4 involvement in osteoarthritis.

Osteoarthritis (OA) is a degenerative chronic disease affecting >300,000 million people around the world as of 2016. Symptomatic measures exist, but there are hardly any curative treatments available. Disruption of the cartilage homeostasis in favor of catabolism leads to cartilage destruction. ROS-macromolecular-induced damage is significantly greater in OA cartilage and OA is described as low-grade chronic systemic inflammation. This review aimed to assess the critical role of cartilage ageing and oxidative stress in the OA process, focusing in particular on NADPH oxidase and especially Nox4 involvement. With age, hypertrophic senescent cells with an altered redox cell profile accumulated. Chondrocytes are more sensitive to oxidant-mediators and the serum level of pro-inflammatory mediators increases. Age-related advanced glycation end products impact on extra cellular matrix (ECM) properties leading to the apoptosis of chondrocytes. A focus on NADPH oxidase-mediated-ROS signaling highlighted the very specific Nox4 isoform, which plays a role on the final common pathway targeting chondrocyte cells. IL-1ß-mediated Nox4 stimulation induced an increase in the levels released by the chondrocyte of MMP-1 and MMP-13 proteins, which are involved in ECM degradation. In comparison with the other Nox isoforms, Nox4 remains unusual, since it is constitutively active, does not depend on cytosolic activator proteins and seems to generate H2O2 thanks to the specific conformation of the Nox4 E-loop. Nox4-induced ROS production appears an essential actor in the OA process and it could be relevant to focus on this target in the aim of discovering and developing new therapeutic strategies.

[Osteofluorosis caused by excess use of toothpaste]. / Ostéose fluorée due à une consommation excessive de dentifrice fluoré.

BACKGROUND: Osteofluorosis is caused by chronic fluoride intoxication. Fluoride is used in toothpaste for the prevention of dental caries, and dental fluorosis has often been reported among children and attributed to ingestion of fluoride toothpaste. We report a case of chronic fluoride intoxication caused by excess use of toothpaste in an adult. CASE: A 45-year-old woman consulted a rheumatologist for painful swelling of the fingers, phalangeal rather than articular. She also had brown staining on her teeth. Radiography of the hands showed periosteal apposition on the phalanges. Further work-up ruled out tumoral or thyroid causes. Laboratory tests showed elevated fluoride levels in the blood (50.9 micromol/L, normal<1.5 micromol/L) and in the urine (721 micromol/L, normal<46 micromol/L). On questioning, we found only one cause for chronic fluoride intoxication: excess and unusual use of toothpaste. The patient brushed her teeth 18 times a day and swallowed the toothpaste, because she liked the taste. She consumed a tube of toothpaste every 2 days, thereby swallowing 68.5 mg of fluoride every day. Suspecting fluorosis from toothpaste, we asked the patient to use a toothpaste without fluoride. Sixteen weeks later, the pain had ceased, and laboratory tests showed massively reduced but still elevated fluoride levels in the blood (6.9 micromol/L) and urine (92.7 micromol/L). CONCLUSION: In this rare case of fluoride intoxication, misuse of a normally innocuous product caused osteofluorosis.

Stability of cardiovascular reactivity to laboratory stressors: a 2 1/2 yr follow-up.

The temporal stability of cardiovascular reactivity to laboratory stressors over a 2 1/2 yr period was studied. Subjects who had earlier received a cold pressor and a shock avoidance reaction time task were brought back for retesting using almost identical tasks. Cardiovascular variables that were common to both sessions included heart rate, systolic and diastolic blood pressure, and pre-ejection period. Correlations were computed to examine the association of responses across both sessions for the four cardiovascular variables during rest and the two tasks. Correlations of both heart rate and systolic blood pressure were high for all tasks and rest, whereas inconsistent correlations were found for diastolic pressure and pre-ejection period. Inconsistencies in diastolic pressure are speculated to be due to individual differences in beta-adrenergic response, whereas lack of consistent pre-ejection period associations may be due to differences in methodology. The results generally support the assumption of stability of cardiovascular reactivity.

Female alcoholic outpatients and female college students: a correlational study of self-reported alcohol consumption and carbohydrate-deficient transferrin levels.

OBJECTIVE: We sought to test the efficacy of two biochemical markers of alcohol consumption, gamma glutamyl transpeptidase and carbohydrate deficient transferrin, as indicators of heavy alcohol consumption in a female population. METHOD: Using a sample of female outpatient alcoholics (n = 36) and a comparison group of female college students (n = 50), alcohol intake was monitored by self-report at approximately 90-day intervals over a period of 12 months. Gamma glutamyl transpeptidase (GGTP) and carbohydrate-deficient transferrin (CDT) values were determined for each sampling period. The criterion for heavy alcohol consumption was set at 140 g/alcohol/week for a 90-day period. Receiver operating characteristic (ROC) curves were plotted, area under the curve (Az) computed, and sensitivity and specificity calculated for both CDT and GGTP. ROC curves provide a graphical illustration of the association between the specificity and sensitivity of any diagnostic test over all possible cutpoint values. RESULTS: A significant, positive correlation between the amount of alcohol consumed and GGTP activity was recorded for the outpatient alcoholic group. Among the college students, there was a significant, positive correlation between CDT levels and alcohol consumed for the second reporting period. The sensitivity of the individual biochemical markers was low but, when used in combination, sensitivity was 66% and specificity, 80%. When a more stringent criterion for heavy alcohol consumption was applied (420 g/alcohol/week), the sensitivity of CDT actually decreased. CONCLUSIONS: CDT, used alone, is a poor indicator of heavy alcohol consumption in female subjects. When GGTP measures are used in conjunction with CDT, detection of heavy alcohol consumption may be enhanced to useful levels.

Alcohol consumption: biochemical and personality correlates in a college student population.

The frequency of alcohol use among a subject population of 28 male and 60 female college students was assessed using the Student Alcohol and Drug Use Survey (STADUS). Data were also collected on personality traits as measured by the Sensation Seeking Scale V (SSSV) and the Eysenck Personality Questionnaire (EPQ). Finally, three biochemical variables were assessed: monoamine oxidase (MAO) activity, dopamine beta hydroxylase (DBH) activity, and testosterone levels. Among males, high SSSV scores, high testosterone levels, and low MAO activity contributed to the variance in alcohol use, whereas among females, a significant proportion of the variability in alcohol use was accounted for by high SSSV scores, high DBH activity, and younger age.

Protective effects of the flavonoid mixture, silymarin, on fetal rat brain and liver.

We investigated the possibility that the flavonoid mixture, silymarin (SY), administered as the compound Silymarin Phytosome (PHYTO), could protect the fetus from maternally ingested EtOH. Seventy-six female rats were randomly assigned to one of seven groups: pair-fed control; chow fed control; EtOH; and four groups receiving EtOH and PHYTO in varying dosages. All groups except the chow-fed control were maintained on a liquid diet. On day 1 of pregnancy the dams began the treatment protocol. On day 21 of pregnancy the rats were sacrificed and the fetuses removed. Gamma glutamyl transpeptidase (GGTP) activity was determined for liver and brain tissue from both the fetuses and the dams. GGTP activity in the EtOH/silymarin treatment groups did not differ significantly from that observed for the pair-fed control group. The observed GGTP activity levels for the EtOH-only group were significantly higher than those attained by the pair-fed control group. Although GGTP activity did not vary significantly with the quantity of PHYTO administered, as PHYTO dose was increased, GGTP activity decreased.

Genetic markers in south african thoroughbred stallions.

Genetically controlled markers are ideal for the identification of individual animals, and throughout the world laboratories have been established whose chief function is to provide a blood-typing service for animals including horses. In order to achieve the aim of improved recording of foals almost all South African sires at stud were tested and their blood type identification completed. The genetic markers included in this survey were 14 blood group factors, transferrin, plasma esterase, haemoglobin, carbonic anhydrase, 6-phosphogluconate dehydrogenase, phosphoglucomutase and phosphohexose isomerase. Gene frequency calculations were performed and comparisons made with similar surveys in Thoroughbreds overseas. The results indicate that the strict selection for speed in Thoroughbred racing horses has resulted in a high degree of genetic uniformity between South African and overseas racing Thoroughbreds.

The usefulness of bone remodelling markers in predicting the efficacy of pamidronate treatment in SAPHO syndrome.

OBJECTIVES: Pamidronate has recently been used in SAPHO syndrome due to its anti-osteoclastic effect. The aim of this study is to determine the usefulness of bone remodelling markers for determining the efficacy of pamidronate treatment. METHODS: Thirteen patients with SAPHO syndrome were treated with pamidronate. The treatment evaluation was done using a visual analogue scale (VAS) and also erythrocyte sedimentation rate, C-reactive protein, serum crosslaps (sCTX) and osteocalcin initially and after 3 months. A relevant clinical response was defined as an improvement in VAS of at least 40%. RESULTS: At 3 months, 7 of 13 patients had a good clinical response, as previously defined. Five of the seven patients maintained the good response over 6 months. Before the first perfusion 6 of the 13 patients had increased sCTX (upper 3250 pmol/l). In this small cohort we tried to analyse whether the increase in bone remodelling markers was associated with a good clinical response. In the responders group the mean levels of sCTX and osteocalcin at baseline were 6783.17 and 24.66, respectively, and in the non-responders group the levels were 2152 and 11.8, respectively. There was a significant difference in sCTX between the responders and the non-responders (P = 0.0044). CONCLUSION: Infusion of pamidronate is effective in SAPHO in some patients. Increased sCTX might be a prognostic marker for a good clinical response but results have to be confirmed in a larger cohort.

The shared epitope is a marker of severity associated with selection for, but not with response to, infliximab in a large rheumatoid arthritis population.

OBJECTIVE: To determine whether joint destruction, indication for, and response to infliximab in rheumatoid arthritis are associated with the shared epitope (SE) or selected cytokine gene polymorphisms (interleukin (IL) 1B, IL1-RN, and tumour necrosis alpha). METHODS: In a large rheumatoid arthritis population of 930 patients from the same area (Rhône-Alpes, France), patients with (n = 198) or without infliximab treatment (n = 732) were compared according to their genetic status. Clinical, biological, and radiological data were collected. Typing for SE status and cytokine polymorphisms was carried out using enzyme linked oligosorbent assay. Statistical analysis was by chi(2) testing and calculation of odds ratios (OR). RESULTS: A dose relation was observed between the number of SE copies and joint damage in the whole rheumatoid population (OR, 1 v 0 SE copy = 2.38 (95% confidence interval, 1.77 to 3.19), p<0.001; OR 2 v 0 SE copy = 3.92 (2.65 to 5.80), p<0.001. The SE effect increased with disease duration but was not significant before two years. Selection for infliximab treatment (n = 198) was associated with increased disease activity, joint damage, and the presence of the SE with a dose effect. In all, 66.2% patients achieved an ACR20 improvement. No clinical or genetic factors were able to predict the clinical response to infliximab. CONCLUSIONS: This post-marketing study in a large cohort of rheumatoid arthritis patients indicates a linkage between rheumatoid arthritis severity, selection for treatment with infliximab, and the presence and dose of the SE.