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ID PMID Title PublicationDate abstract
20173392 TNF and bone. 2010 Bone is subject to permanent remodeling during development and through life. This activity is essential for (a) proper shaping and growth of each bone during development; (b) maintenance of bone mass as well as structural integrity of the micro architecture of bone through adult life, and (c) tissue repair needed for healing of fracture as well as of micro-damage. In addition to genetically linked rare developmental diseases, disturbances in bone remodeling are causing common bone pathologies, which severely impair the quality of life of patients. Among them are postmenopausal osteoporosis and local as well as systemic bone loss observed in chronic inflammatory diseases such as rheumatoid arthritis. The role of TNF-alpha in mediating bone remodeling will be presented and discussed in this chapter.
20018049 Evaluation of an optimal receiver operating characteristic procedure. 2009 Dec 15 : Lu and Elston have recently proposed a procedure for developing optimal receiver operating characteristic curves that maximize the area under a receiver operating characteristic curve in the setting of a predictive genetic test. The method requires only summary data, not individual level genetic data. In an era of increased data sharing, we investigate the performance of this algorithm when individual level genetic data are available and compare this approach to more standard receiver operating characteristic curve-building methods. CONCLUSION: Though the Lu-Elston method can produce an optimal area under the curve under some assumptions, the method typically has little advantage over standard multivariable logistic methods when data are available. Also, the standard approach easily allows comparison of nested models via likelihood ratio tests and incorporation of covariates - the Lu-Elston approach is shown to have some difficulties with such analyses. These conclusions are based on evaluations using the Genetic Analysis Workshop 16 rheumatoid arthritis data set.
19559484 Expression and role of CR1 and CR2 on B and T lymphocytes under physiological and autoimmu 2009 Sep The involvement of complement in the development and regulation of antibody responses under both healthy and pathological conditions is known for long. Unravelling the molecular mechanisms underlying the events however is still in progress. This review focuses on the role of complement receptors CR1 (CD35) and CR2 (CD21) expressed on T and B cells. Alteration in the expression and function of these receptors may contribute to the initiation and maintenance of immune complex mediated autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Recent data regarding complement receptor expression on T lymphocytes and on memory B cells are also discussed.
19152092 The impact of rheumatic diseases on sexual function. 2009 Jun Sexuality is a complex aspect of the human being's life and is more than of only the sexual act. Normal sexual functioning consists of sexual activity with transition through the phases from arousal to relaxation with no problems, and with a feeling of pleasure, fulfillment and satisfaction. Rheumatic diseases may affect all aspects of life including sexual functioning. The reasons for disturbing sexual functioning are multifactorial and comprise disease-related factors as well as therapy. In rheumatoid arthritis and ankylosing spondylitis patients, pain and depression could be the principal factors contributing to sexual dysfunction. On the other hand, in women with Sjögren's syndrome, systemic lupus erythematosus and systemic sclerosis sexual dysfunction is apparently most associated to vaginal discomfort or pain during intercourse. Finally, sexual dysfunction in patients with fibromyalgia could be principally associated with depression, but the characteristic symptoms of fibromyalgia (generalized pain, stiffness, fatigue and poor sleep) may contribute to the occurrence of sexual dysfunction. The treatment of sexual dysfunction will depend on the specific patient's symptoms, however, there are some general recommendations including: exploring different positions, using analgesics drug, heat and muscle relaxants before sexual activity and exploring alternative methods of sexual expression. This is a systemic review about the impact of several rheumatic diseases on sexual functioning. There are no previous overviews about this topic so far.
19129679 Peroxisome proliferator-activated receptor gamma and cardiovascular diseases. 2009 Feb Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily and form heterodimers with retinoid X receptor. Three PPAR isoforms have been isolated and termed alpha, beta (or delta) and gamma. Although PPARgamma is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, PPARgamma is also present in a variety of cell types. Synthetic antidiabetic thiazolidinediones (TZDs) are well known as ligands and activators for PPARgamma. After it was reported that activation of PPARgamma suppressed production of pro-inflammatory cytokines in activated macrophages, medical interest in PPARgamma has grown and there has been a huge research effort. PPARgamma is currently known to be implicated in various human chronic diseases such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimer's disease. Many studies suggest that TZDs not only ameliorate insulin sensitivity, but also have pleiotropic effects on many tissues and cell types. Although activation of PPARgamma seems to have beneficial effects on cardiovascular diseases, the mechanisms by which PPARgamma ligands prevent their development are not fully understood. Recent data about the actions and its mechanisms of PPARgamma-dependent pathway in cardiovascular diseases are discussed here.
19118972 Fatigue communication at the out-patient clinic of Rheumatology. 2009 Jul OBJECTIVE: To describe nurse-patient and rheumatologist-patient interaction in fatigue communication at the rheumatology out-patient clinic. METHODS: Consultations of 20 rheumatoid arthritis (RA) patients with the nurse specialist and the rheumatologist were videotaped and analysed using the Medical Interview Aural Rating Scale (MIARS). Subsequently, patients were asked to fill out a concern questionnaire asking how worried they felt and how satisfied they were with attention given by both healthcare professionals. Finally, patients were interviewed on reasons for being not or not completely satisfied with the care received. RESULTS: Fatigue was discussed in 42% of the rheumatologists' consultations and 83% of the nurse specialists' consultations. RA patients more often used implicit cues instead of explicit concerns related to fatigue. Almost 72% of the patients felt worried about fatigue and in general they were more satisfied with the nurse specialist's attention to fatigue than with the attention from the rheumatologist. CONCLUSION: Fatigue is not structurally communicated at the rheumatology out-patient clinic and exploring and acknowledging communication techniques can help patients to express their concerns about fatigue. PRACTICE IMPLICATIONS: Healthcare professionals must recognise fatigue as a severe problem for RA patients and start the conversation on fatigue instead of waiting for the patient to mention fatigue spontaneously.
20737185 Successful treatment of steroid-resistant methotrexate-induced interstitial pneumonia with 2011 Feb A 76-year-old woman with rheumatoid arthritis who had been taking methotrexate (MTX) for 9 months was admitted because of acute respiratory failure. A chest radiograph revealed diffuse ground-glass attenuation. MTX-induced interstitial pneumonia (IP) was strongly suspected. Her respiratory failure worsened in spite of steroid pulse therapy. Intravenous administration of ulinastatin, however, dramatically improved her clinical condition. The second ulinastatin treatment was also effective. This case suggests that peripherally administered ulinastatin may be effective for steroid-resistant MTX-induced IP.
20625488 Anti-TNF-alpha therapies in systemic lupus erythematosus. 2010 Tumor necrosis factor (TNF)-alpha is not just a proinflammatory cytokine. It has also been proposed to be an immunoregulatory molecule that can alter the balance of T regulatory cells. Anti-TNF-alpha therapies have been provided clinical benefit to many patients and introduced for treating moderate to severe rheumatoid arthritis, Crohn's disease, and other chronic inflammatory disorders. However, their use also is accompanied by new or aggravated forms of autoimmunity, such as formation of autoantibodies, including antinuclear antibodies (ANAs), antidouble-stranded DNA (dsDNA) antibodies, and anticardiolipin antibodies (ACL). Systemic lupus erythematosus (SLE) is a disease with autoimmune disturbance and inflammatory damage. The role of TNF-alpha in human SLE is controversial. Here we review the role of TNF-alpha in the pathophysiological processes of SLE and the likely effects of blocking TNF-alpha in treatment of SLE.
20077080 Quantitation of ibuprofen in blood using gas chromatography-mass spectrometry (GC-MS). 2010 Ibuprofen is a non-narcotic, non-steroidal anti-inflammatory drug used for the treatment of pain, fever, and inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. It is also used for induction of closure of patent ductus arteriosus (PDA) in neonates. Although the exact mechanism of action of ibuprofen is not known, it is believed to mediate its therapeutic effects through the inhibition of cyclooxygenase and subsequently by the inhibition of prostacyclin production. As the drug has a number of side effects, which correlate to its circulating concentration, monitoring of ibuprofen in plasma or serum is desired for patients receiving high-dose therapy. Chromatographic methods are frequently used for the assay of ibuprofen, as no immunoassays are currently available.In the method described, the drug is extracted from the serum or plasma using methylene chloride and phosphate buffer (pH 6). Meclofenamic acid is used as an internal standard. The organic phase containing the drug is separated and dried under stream of nitrogen. After trimethylsilyl derivatization, analysis is done using gas-chromatography/ mass spectrometry (GC-MS). Quantification of the drug in a sample is achieved by comparing responses of the unknown sample to the responses of the calibrators using selected ion monitoring.
20525843 EULAR points to consider when establishing, analysing and reporting safety data of biologi 2010 Sep OBJECTIVES: The introduction of biological therapies for the treatment of rheumatic diseases has drawn attention to the limitations of traditional means of assessing drug safety. Consequently, a series of European academic biologics registers dedicated to this task have been established. Increasing reliance upon safety data generated from observational drug registers makes it important to convert the lessons learned from such registers into recommendations for rheumatologists embarking upon the establishment of future registers, or analysing and reporting from new and existing registers. METHODS: The Task Force encompassed 11 scientists from European Rheumatology drug registers. Through an informal inventory of critical elements in the establishment of existing rheumatoid arthritis drug registers, of analytical strategies used and of limitations of their results, several 'points to consider'--beyond established generic guidelines for observational registers/studies but with particular relevance to biologics registers on safety in rheumatology--were assembled. For each 'point to consider', contextual and methodological background and examples were compiled. RESULTS: A set of seven points to consider was assembled for the establishment of new drug registers with a focus on purpose, population to be targeted, data collection, handling and storage as well as ethical and legal considerations. For analysis and reporting, nine points to consider were assembled (setting, participant, variable, statistical method, descriptive data, outcome data, main results, other analyses and limitations). CONCLUSIONS: Thoughtful design and planning before the establishment of biologics registers will increase their sustainability, versatility and raw data quality. Harmonisation of analyses and reporting from such registers will improve interpretation of drug safety studies.
19479824 Remnants of secondarily necrotic cells fuel inflammation in systemic lupus erythematosus. 2009 Jun OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are often characterized by cellular as well as humoral deficiencies in the recognition and phagocytosis of dead and dying cells. The aim of this study was to investigate whether the remnants of apoptotic cells are involved in the induction of inflammatory cytokines in blood-borne phagocytes. METHODS: We used ex vivo phagocytosis assays comprising cellular and humoral components and phagocytosis assays with isolated granulocytes and monocytes to study the phagocytosis of secondarily necrotic cell-derived material (SNEC). Cytokines were measured by multiplex bead array technology. RESULTS: We confirmed the impaired uptake of various particulate targets, including immunoglobulin-opsonized beads, by granulocytes and monocytes from patients with SLE compared with healthy control subjects. Surprisingly, blood-borne phagocytes from two-thirds of the patients with SLE took up SNEC, which was rarely phagocytosed by phagocytes from healthy control subjects or patients with rheumatoid arthritis. Supplementation of healthy donor blood with IgG fractions derived from patients with SLE transferred the capability to take up SNEC to the phagocytes of healthy donors. Phagocytosis-promoting immune globulins also induced secretion of huge amounts of cytokines by blood-borne phagocytes following uptake of SNEC. CONCLUSION: Opsonization of SNEC by autoantibodies from patients with SLE fosters its uptake by blood-borne monocytes and granulocytes. Autoantibody-mediated phagocytosis of SNEC is accompanied by secretion of inflammatory cytokines, fueling the inflammation that contributes to the perpetuation of autoimmunity in SLE.
19333976 A rheumatology-specific informatics-based application with a disease activity calculator. 2009 Apr 15 OBJECTIVE: To design a rheumatology-specific tool with a disease activity calculator integrated into the electronic medical records (EMRs) at our institution and assess physicians' attitudes toward the use of this tool. METHODS: The Rheumatology OnCall (ROC) application culls rheumatology-pertinent data from our institution's laboratory, microbiology, pathology, radiology, and pharmacy information systems. Attending rheumatologists and rheumatology fellows accessed the ROC and disease activity calculator during outpatient visits at the time of the clinical encounter. RESULTS: During the 12-week study period, 15 physicians used the ROC application and the disease activity calculator during 474 and 429 outpatient clinic visits, respectively. In weekly survey responses, physicians reported that use of the ROC interface improved patient care in 140 (78%) of 179 visits, and that the Disease Activity Score in 28 joints (DAS28) results at the time of the visit would not have changed patient management in 157 (88%) of these, although seeing a trend in DAS28 was useful in 149 (96%) of 156 visits. At the study's conclusion, most physicians reported that the ROC application was useful (11 of 12 physicians) and that seeing a trend in DAS28 improved daily patient care (12 of 13 physicians). CONCLUSION: The ROC application is useful in daily rheumatologic care, and the disease activity calculator facilitates management of patients with rheumatoid arthritis. However, widespread acceptance and use of such tools depend upon the general acceptance of and access to EMRs in the clinical setting. The utility of the disease activity calculator may be limited by the lack of available acute-phase reactant results at the time of the clinical encounter.
19155499 Complement inhibitor C4b-binding protein interacts directly with small glycoproteins of th 2009 Feb 1 Components derived from cartilage have been suggested to maintain the inflammation in joints in arthritis. Small leucine-rich repeat proteins (SLRPs) are structural components of cartilage important in organizing the meshwork of extracellular matrix components. It has recently been shown that the SLRP fibromodulin interacts with complement initiator C1q, leading to complement activation. The complement response is limited since fibromodulin also interacts with the complement inhibitor factor H. We have now found that osteoadherin, chondroadherin, fibromodulin, and proline arginine-rich end leucine-rich repeat protein bind to the complement inhibitor C4b-binding protein (C4BP). Using direct binding assays with C4BP fragments and C4BP mutants lacking individual domains in combination with electron microscopy, we have demonstrated that mainly the central core of C4BP mediated binding to SLRPs. Binding of SLRPs to C4BP did not affect its ability to inhibit complement. Osteoadherin, fibromodulin, and chondroadherin, which bind C1q and activate complement, were found to cause significantly higher C9 deposition in C4BP-depleted serum compared with Igs, indicating that the level of complement activation initiated by SLRPs is regulated by simultaneous binding to C4BP. A similar dual binding of C1q and complement inhibitors was observed previously for other endogenous ligands (amyloid, prions, C-reactive protein, and apoptotic cells) but not for exogenous activators (bacteria-bound Igs). These interactions can be significant during inflammatory joint diseases, such as rheumatoid arthritis, where cartilage is degraded, and cartilage components are released into synovial fluid, where they can interact with factors of the complement system.
19121415 Heat-shock proteins can promote as well as regulate autoimmunity. 2009 Mar Heat-shock proteins (Hsps) are among the most highly conserved and immunogenic proteins shared by microbial agents and mammals. Under physiological conditions, the ubiquitously distributed Hsps maintain the integrity and function of other cellular proteins when cells are exposed to stressful stimuli. However, owing to their conserved nature and stress inducibility, Hsps may become targets of immune response. The T cells and/or antibodies induced by a microbial Hsp may crossreact with the corresponding mammalian Hsp (molecular mimicry) and trigger an autoimmune response, which if unchecked can lead to immune pathology and clinical manifestations. Furthermore, enhanced expression of Hsp under stress can unveil previously hidden antigenic determinants that can initiate and perpetuate autoimmune reactivity. Also, the innate immune mechanisms activated by an Hsp can reinforce and even direct the type of adaptive immune response to that protein. Hsps have been implicated in the induction and propagation of autoimmunity in several diseases, including rheumatoid arthritis, atherosclerosis and type 1 diabetes. However, Hsps possess immunoregulatory attributes as well and therefore, are being exploited for immunomodulation of various immune-mediated disorders.
20678963 The use of adjuvant high-dose-rate breast brachytherapy in patients with collagen vascular 2011 Mar PURPOSE: To analyze toxicity and cosmesis in patients with collagen vascular disease (CVD) treated with accelerated partial breast irradiation (APBI) via high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: This is a pooled analysis of patients with early stage and in situ breast cancer with CVD treated with adjuvant multicatheter or balloon brachytherapy. Physicians at multiple institutions were asked to review their experience and report data regarding toxicity and cosmesis in patients with CVD. All patients fit American Society of Breast Surgeons recommendations for APBI and were treated with HDR brachytherapy with ≥ 3 months followup. RESULTS: Nine cases from five institutions are the subject of this analysis. The median patient age was 54 years and median followup was 31 months. All patients had documented history and active signs/symptoms of rheumatoid arthritis, systemic lupus erythematosis, psoriatic arthritis, or scleroderma. All patients had received medical therapy for CVD in the past, and 78% were under active treatment at the time of brachytherapy. All the patients were treated with multicatheter or balloon (MammoSite [Hologic, Inc., Marlboro, MA], MammoSite ML [Hologic, Inc., Marlboro, MA], or Contura [Senorx, Irvine, CA]) brachytherapy with a median volume of 45.5 cc and a median skin distance of 7.5mm. Acute toxicity included Grade 1 skin erythema (5) and catheter-site wound dehiscence (1). Late toxicity included seroma (5), induration (5), pain (2), telangectasia (2), and superficial infection (1). Cosmesis was excellent or good for all the patients. CONCLUSIONS: Women with CVD have a toxicity and cosmesis profile consistent with other APBI series. Although confirmatory data is needed, it may not be necessary to exclude these patients from clinical trials of APBI.
20089308 Sinomenine, theophylline, cysteine, and levamisole: Comparisons of their kinetic effects o 2010 Apr The effects of sinomenine (SIN, an alkaloid extracted from the Chinese medicinal plant Sinomenium acutum used for centuries to treat rheumatic disease, including rheumatoid arthritis) on apatitic nucleation and matrix vesicle (MV)-induced mineral formation were compared with those of cysteine, levamisole, and theophylline. We found that SIN was not an inhibitor of tissue non-specific alkaline phosphatase (TNAP), a marker of biological mineralization, but confirmed that cysteine, levamisole, and theophylline were. Further, none of these four molecules directly affected the nucleation of hydroxyapatite (HA) formation, in contrast to pyrophosphate (PP(i)) which did. Incubation of 0.25-1.0mM cysteine, theophylline, or levamisole with MVs in synthetic cartilage lymph (SCL) containing AMP and Ca(2+), but not inorganic phosphate (P(i)), prolonged the induction time of mineral formation, apparently by inhibiting TNAP activity. SIN at the same levels neither inhibited TNAP activity nor affected the induction time of MV mineral formation. However, SIN did markedly delay MV-induced mineral formation in SCL containing P(i) (instead of AMP) in a manner similar to theophylline, but to a lesser extent than levamisole. Cysteine did not delay, in fact it slightly accelerated MV-induced mineral formation in Pi-containing SCL. These findings suggest that levamisole, SIN and theophylline may directly affect Ca(2+) and/or P(i) accretion during mineral formation; however, TNAP was not directly involved. The possible roles of annexins and other ion transporters, such as proteins of the solute carrier family implicated in Ca(2+) and P(i) influx are discussed.
20429850 Targeting lymphocyte co-stimulation: from bench to bedside. 2010 Nov T and B lymphocytes are central regulators and effectors of immune responses and are believed to have a key role in many autoimmune diseases. Targeting the activation or effector function of lymphocytes is a potentially effective approach to treat autoimmunity. Typically, T-cell activation occurs after engagement of the T-cell receptor with its cognate peptide-major histocompatibility complex (signal 1) and subsequent engagement of co-stimulatory molecules (signal 2). This "second signal" contributes to T-cell activation by promoting proliferation, survival, and effector function. In general, activation in the absence of co-stimulation leads to a reduced immune response, anergy, or even tolerance. B-cell activation similarly requires co-stimulation for the development of complete effector function. The most potent co-stimulatory molecules identified to date are CD28 for T-cells and CD40 for B-cells. Both molecules are recognized for their potential as immune modulators; however, thus far neither molecule has been successfully targeted directly for the treatment of autoimmune disease. The only current therapy to target either of these pathways is cytotoxic T-lymphocyte antigen-4 (CTLA-4-Ig), which indirectly blocks CD28 signaling and has proven efficacy in rheumatoid arthritis and juvenile idiopathic arthritis patients. In addition to CD28 and CD40, an array of other co-stimulatory as well as inhibitory pathways has recently been identified and scientists are just beginning to understand how these different signaling pathways interact to regulate lymphocyte activation. In the more than two decades since the discovery of the first co-stimulatory molecule, the full clinical potential of these pathways is yet to be realized. In this review, we will primarily focus on CD28 and CD40 which are the most clinically validated co-stimulatory pathways, and briefly summarize and discuss some of the other T-cell co-stimulatory molecules.
21618832 CD97 in leukocyte trafficking. 2010 CD97 is a member of the EGF-TM7 family of adhesion G protein-coupled receptors (GPCRs) broadly expressed on leukocytes. CD97 interacts with several cellular ligands via its N-terminal epidermal growth factor (EGF)-like domains. To understand the biological function of CD97, monoclonal antibodies (mAbs) specific for individual EGF domains have been applied in a variety of in vivo models in mice, which represent different aspects of innate and adaptive immunity. Targeting CD97 by mAbs inhibited the accumulation of neutrophilic granulocytes at sites of inflammation thereby affecting antibacterial host defense, inflammatory disorders and stem cell mobilization from bone marrow. Interestingly, targeting CD97 did not impact antigen-specific (adaptive response) models such as delayed type hypersensitivity (DTH) or experimental autoimmune encephalomyelitis (EAE). However, collagen-induced arthritis (CIA), a model for rheumatoid arthritis, was significantly ameliorated suggesting therapeutic value of CD97 targeting. CD97-deficient mice are essentially normal at steady state except for a mild granulocytosis, which increases under inflammatory conditions. Comparison of the consequences of antibody treatment and gene targeting implies that CD97 mAbs actively inhibit the innate response presumably at the level of granulocyte or macrophage recruitment to sites of inflammation. Based on the collected data, we propose that the CD97 mAbs either activate CD97-mediated signal transduction via a yet unknown mechanism or act by inducing CD97 internalization, making CD97 unavailable for binding to its ligands and thereby blocking recruitment of neutrophils and possibly macrophages.
21050433 Enhanced angiogenic potency of monocytic endothelial progenitor cells in patients with sys 2010 INTRODUCTION: Microvasculopathy is one of the characteristic features in patients with systemic sclerosis (SSc), but underlying mechanisms still remain uncertain. In this study, we evaluated the potential involvement of monocytic endothelial progenitor cells (EPCs) in pathogenic processes of SSc vasculopathy, by determining their number and contribution to blood vessel formation through angiogenesis and vasculogenesis. METHODS: Monocytic EPCs were enriched and enumerated using a culture of peripheral blood mononuclear cells and platelets on fibronectin in 23 patients with SSc, 22 patients with rheumatoid arthritis (RA), and 21 healthy controls. To assess the capacity of monocytic EPCs to promote vascular formation and the contribution of vasculogenesis to this process, we used an in vitro co-culture system with human umbilical vein endothelial cells (HUVECs) on Matrigel® and an in vivo murine tumor neovascularization model. RESULTS: Monocytic EPCs were significantly increased in SSc patients than in RA patients or healthy controls (P = 0.01 for both comparisons). Monocytic EPCs derived from SSc patients promoted tubular formation in Matrigel® cultures more than those from healthy controls (P = 0.007). Transplantation of monocytic EPCs into immunodeficient mice resulted in promotion of tumor growth and blood vessel formation, and these properties were more prominent in SSc than healthy monocytic EPCs (P = 0.03 for both comparisons). In contrast, incorporation of SSc monocytic EPCs into the tubular structure was less efficient in vitro and in vivo, compared with healthy monocytic EPCs. CONCLUSIONS: SSc patients have high numbers of aberrant circulating monocytic EPCs that exert enhanced angiogenesis but are impaired in vasculogenesis. However, these cells apparently cannot overcome the anti-angiogenic environment that characterizes SSc-affected tissues.
19822073 Tumor necrosis factor-alpha antagonists: differential clinical effects by different biotec 2009 Jul Inhibitors of tumor necrosis factor-alpha have deeply changed the therapy of several inflammatory human diseases. For instance, clinical management of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis have profoundly benefited after the introduction of new therapeutic tools, such as antagonist of TNF-alpha molecule. These drugs include etanercept, a soluble TNF-alpha receptor antagonist, three anti-TNF-alpha antibodies, adalimumab, infliximab, golimumab and certolizumab a humanized Fab fragment combined with polyethylene glycol. These compounds efficiently inhibit several TNF-alpha biological-mediated effects, however, they have also shown differential clinical efficacy in several trials from different autoimmune diseases. It is of clinical relevance that non-responders to one of these drugs often positively responded to another. Different mechanisms of action and diversity in pharmacokinetics of these three compounds may partially explain different clinical effects. However, partially diverse pathogenetic mechanisms in different diseases also contribute to differential therapeutic responses. Therefore, these apparently homogeneous agents can not be considered equivalent in their clinically efficacy. Differential therapeutic actions of these drugs may be advantageously used in clinical practice and further improve the great potential of individual TNF-alpha inhibitors.