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ID PMID Title PublicationDate abstract
22736090 Prevalence of interferon type I signature in CD14 monocytes of patients with Sjogren's syn 2013 May OBJECTIVE: To determine the prevalence of upregulation of interferon (IFN) type I inducible genes, the so called 'IFN type I signature', in CD14 monocytes in 69 patients with primary Sjögren's syndrome (pSS) and 44 healthy controls (HC) and correlate it with disease manifestations and expression of B cell activating factor (BAFF). METHODS: Expression of IFI44L, IFI44, IFIT3, LY6E and MX1 was measured using real time quantitative PCR in monocytes. Expression values were used to calculate IFN type I scores for each subject. pSS patients positive for the IFN type I signature (IFN score≥10) and patients negative for the signature (IFN score<10) were then compared for clinical disease manifestations and BAFF expression. A bioassay using a monocytic cell line was performed to study whether BAFF mRNA expression was inducible by IFN type I activity in serum of patients with pSS. RESULTS: An IFN type I signature was present in 55% of patients with pSS compared with 4.5% of HC. Patients with the IFN type I signature showed: (a) higher EULAR Sjögren's Syndrome Disease Activity Index scores; higher anti-Ro52, anti-Ro60 and anti-La autoantibodies; higher rheumatoid factor; higher serum IgG; lower C3, lower absolute lymphocyte and neutrophil counts; (b)higher BAFF gene expression in monocytes. In addition, serum of signature-positive patients induced BAFF gene expression in monocytes. CONCLUSIONS: The monocyte IFN type I signature identifies a subgroup of patients with pSS with a higher clinical disease activity together with higher BAFF mRNA expression. Such patients might benefit from treatment blocking IFN type I production or activity.
25419541 Characterization of DC-STAMP+ Cells in Human Bone Marrow. 2013 Jul 19 Osteoclasts (OC), specialized cells derived from monocytes, maintain skeletal homeostasis under normal conditions but degrade bone in patients with rheumatoid (RA) and psoriatic arthritis (PsA). Monocytes initially develop in the bone marrow (BM), circulate in peripheral blood, and differentiate into distinct cell types with diverse functions. Imaging studies in (RA) patients and murine arthritis models demonstrate that bone marrow edema detected on MRI is the result of enhanced myelopoiesis which precedes the development of bone erosions detected on plain radiographs several years later. A major knowledge gap, however, is whether OC develop in the BM and circulate to the joint and if the differentiation to OC takes place in the joint space in response to differentiation signals such as RANKL and TNF. We have previously demonstrated that osteoclast precursors (OCP) are increased in the circulaton of patients with RA and PsA. We showed that DC-STAMP (Dendritic Cell-Specific Transmembrane protein), a 7-pass transmembrane protein expressed on the surface of monocytes, is essential for cell-to-cell fusion during OC differentiation and is a valid biomarker of OCP. Herein, we examined OCP in human bone marrow and identified one novel subset of DC-STAMP+CD45(intermediate) monocytes which was absent in the blood. We also found that OCPs reside in human BM with a higher frequency than in the peripheral blood. These findings support the notion that the BM is a major reservoir of circulating OCPs. In addition, we demonstrated that a higher frequency of DC-STAMP+ cells in the BM have detectable intracellular IFN-γ, IL-4 and IL-17A than DC-STAMP+ cells circulating in the peripheral blood. Finally, the frequency of DC-STAMP+ monocytes and T cells is signficantly higher in PsA BM compared to healthy controls, suggesting an enhanced myelopoiesis is a central event in inflammatory arthritis.
23917390 High-dose methylprednisolone pulse therapy upregulated FcγRIIb expression on B cells in p 2013 Dec Abnormalities in B cell are characteristic feature of primary Sjögren's syndrome (pSS). As FcγRIIb is a key regulator of B cells, the objective of this study is to investigate the role of the inhibitory receptor FcγRIIb in B cells from pSS patients, and whether glucocorticoid can affect B cell subpopulations or FcγRIIb expression. Thirty pSS patients and 15 healthy controls were enrolled in this study. The results showed that the percentage of memory CD19(+)CD27(+) B cells was significantly lower in pSS patients compared to in healthy controls. FcγRIIb expression on memory CD19(+)CD27(+) B cells from active pSS patients was significantly reduced compared with those from inactive or healthy controls. The level of FcγRIIb on memory CD19(+)CD27(+) B cells from active pSS patients was negatively correlated with anti-SSA antibody titers and Sjögren's syndrome disease activity index. After a high-dose methylprednisolone pulse therapy for 3 days, FcγRIIb expression on memory B cells was upregulated, with the raised level of platelets. In vitro, dexamethasone could elevate FcγRIIb expression on B cells of pSS patients in a dose-dependent manner. Taken together, our data suggest that the upregulation of FcγRIIb may be expected to be a new therapeutic strategy in pSS patients.
25065014 In vitro immunomodulatory effects of microencapsulated umbilical cord Wharton jelly-derive 2015 Jan OBJECTIVE: Human umbilical cord Wharton jelly-derived mesenchymal stem cells (hUCMS) are easy to retrieve in bulk. They may interact with immune cells by either cell contact or soluble factors. Little evidence is currently available on potential therapeutic application of hUCMS to systemic autoimmune disorders such as primary SS (pSS). We have recently developed an endotoxin-free alginate gel that can be used to microencapsulate different cell types for graft into non-immunosuppressed hosts. We aimed to assess the in vitro effects of IFN-γ-pretreated microencapsulated (CpS)-hUCMS on T cells of pSS. METHODS: Ten pSS patients and 10 healthy donors were selected. Peripheral blood mononuclear cells (PBMCs) were obtained from venous blood to establish co-cultures with CpS-hUCMS. Lymphocyte proliferation and phenotypic analysis was performed by flow cytometry and real-time PCR on IFN-γ-pretreated hUCMS was performed before PBMCs co-culture. RESULTS: We found that CpS-hUCMS suppress pSS T cell proliferation and restore the Treg/Th17 ratio, thereby possibly positively impacting the pSS disease process. CONCLUSION: We have developed a new biohybrid drug delivery system that now waits for clinical application in autoimmune diseases, including pSS.
24636281 [Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases]. 2015 Jan 20 Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use.
24635953 [Normal skin biopsy as a tool for extra-cutaneous disorders]. 2014 Mar Biopsies of apparently healthy skin can contribute to the diagnosis of an internal disorder in a patient or in the detection of a potential disease carrier. Herein, we review those diseases for which dermatologists may be asked to perform a biopsy on normal skin where analysis by optical microscopy, immunofluorescence or electronic microscopy may result in diagnosis of an "internal" disease. Diseases for which biopsies are required for cell cultures (e.g. fibroblasts cultures), clonality testing or chromosomal analysis are not discussed here.
23831963 MxA as a clinically applicable biomarker for identifying systemic interferon type I in pri 2014 Jun OBJECTIVE: To establish an easy and practical assay for identifying systemic interferon (IFN) type I bioactivity in patients with primary Sjögren's syndrome (pSS). The IFN type I signature is present in over half of the pSS patients and identifies a subgroup with a higher disease activity. This signature is currently assessed via laborious expression profiles of multiple IFN type I-inducible genes. METHODS: In a cohort of 35 pSS patients, myxovirus-resistance protein A (MxA) was assessed as a potential biomarker for type I IFN activity, using an enzyme immunoassay (EIA) on whole-blood and flow cytometric analyses (fluorescence-activated cell sorting, FACS) of isolated CD14 monocytes. In addition, potential biomarkers such as CD64, CD169 and B cell-activating factor (BAFF) were simultaneously analysed in CD14 monocytes using FACS. The IFNscore, a measure for total type I IFN bioactivity, was calculated using expression values of the IFN type I signature genes--IFI44, IFI44L, IFIT3, LY6E and MX1--in CD14 monocytes, determined by real-time quantitative PCR. RESULTS: IFNscores correlated the strongest with monocyte MxA protein (r=0.741, p<0.001) and whole-blood MxA levels (r=0.764, p<0.001), weaker with CD169 (r=0.495, p<0.001) and CD64 (r=0.436, p=0.007), and not at all with BAFF protein. In particular, whole blood MxA levels correlated with EULAR Sjögren's Syndrome Disease Activity Index scores and numerous clinical pSS parameters. Interestingly, patients on hydroxychloroquine showed reduced MxA levels (EIA, p=0.04; FACS p=0.001). CONCLUSIONS: The MxA assays were excellent tools to assess IFN type I activity in pSS, MxA-EIA being the most practical. MxA levels associate with features of active disease and are reduced in hydroxychloroquine-treated patients, suggesting the clinical applicability of MxA in stratifying patients according to IFN positivity.
25229497 Size matters--nanotechnology and therapeutics in rheumatology and immunology. 2014 Nanotechnology, or the use of technology at the submicron scale, and its application to medicine (nanomedicine) draws from many ideas and technological advancements across myriad fields of materials technology and has improved biomedical understanding. Nanotechnology puts current materials science on the same physical scale as classic immune mediating substances, including viruses, moieties found on prokaryotic bacteria, and antigen presenting cells. Functionalized nanoparticles, fullerenes, liposomes, nanogels, and virus-like particles, are several examples of nanotechnology that are currently being applied to the treatment of oncologic and infectious diseases. However, the majority of the current commercial utilization of nanomedicine has been directed towards creating improved vaccines in order to prevent infectious diseases. These processes may have direct applications toward the creation of vaccines used to treat autoimmune disease as well. Current therapeutics utilizing nanotechnology, are gaining traction in treatments for gout and rheumatoid arthritis, and experimental animal models have demonstrated success in using the above technologies to improve the effectiveness and safety of current standard treatment of rheumatologic illnesses. Here we review many of the common forms of nanoparticles used in medical applications as well as where they have found a role in rheumatology. Continued technical feasibility, ongoing safety studies, and lingering questions on cost are all issues that have not yet been resolved in regards to widespread application in rheumatology and immunology.
25198242 Is atherosclerosis accelerated in systemic sclerosis? Novel insights. 2014 Nov PURPOSE OF REVIEW: During the last few decades, the death rate due to cardiovascular disease in systemic sclerosis (SSc) patients has substantially increased. Whether this is because of accelerated atherosclerosis, similar to what has been demonstrated in rheumatoid arthritis and systemic lupus erythematosus, remains to be established. In this review, the main recent evidence about potential pathogenic mechanisms of accelerated atherosclerosis, microvascular disease and macrovascular disease in SSc, and the results from the surrogate measures for detecting and quantifying subclinical atherosclerosis in SSc patients are reviewed. RECENT FINDINGS: Significantly higher risk of coronary heart disease in SSc patients compared with the general population has been found in the largest cohort studies. However, no difference in either atherosclerotic plaque occurrence or intima-media thickness was detected. The diagnostic utility of other techniques, such as cardiac MRI, in order to improve detection and characterization of SSc heart disease remains to be determined. SUMMARY: Although microvascular disease is a hallmark of SSc, mechanistic insights explaining the presence of accelerated atherosclerosis, and the presence and extent of macrovascular disease in SSc patients are lacking. Future challenges will be to unravel the genetic, environmental and ethnic determinants of such processes.
25161969 Ankle and foot tuberculosis: a diagnostic dilemma. 2014 Apr AIM AND OBJECTIVE: To know the biological behavior of ankle and foot tuberculosis (AFTB) and to know the reasons for delay in diagnosis and treatment of AFTB in our population. MATERIALS AND METHODS: Patients with non-healing ulcers/sinuses/swellings in the ankle and foot region are the subjects of present study. Detailed clinical history, physical examination and relevant investigations were done in all cases. Pus/wound discharge for acid fast bacillus (AFB) study and biopsy from wound margin/sinus tract was taken in all the cases. RESULTS: During the period from July 2007-June 2012, 20 cases of AFTB were treated. Out of them five cases were difficult to diagnose and a mean period of 6 month to 5year was elapsed before final diagnosis was established. Out of these five cases - three cases were diabetic with ulcers and sinuses in the heel and ankle region. One case was wrongly diagnosed as angiodysplasia with A-V malformation of foot and diagnosis was delayed for 5 year. In one case of rheumatoid arthritis with abscess in ankle joint, the diagnosis was delayed for 1year. CONCLUSION: AFTB is very rare condition. AFTB is suspected in cases with long standing pain/swelling/discharging sinus in the foot and thorough investigations is must to differentiate from other foot diseases. Diagnosis is delayed due to lack of clinical suspicion and non-confirmatory biopsy reports. Early diagnosis and ATT for 9-18 months is must in all cases of AFTB to prevent joint involvement and other complications.
25159162 Pharmacological intervention at CCR1 and CCR5 as an approach for cancer: help or hindrance 2014 While a number of agents directed at chemokine receptors have entered clinic trials, the vast majority of these have failed, and the enthusiasm for this class of drugs has been attenuated. To date, there are two drugs that inhibit chemokine receptors approved by the FDA. The first to be approved in 2007 was maraviroc (brand name Selzentry, or Celsentri outside the US) which targets CCR5 and is used for the treatment of HIV infection. The second is plerixafor (Mozobil) which was approved in 2008, targets CXCR4, and is used for the mobilization of hematopoietic stem cells. This review will focus on the CC chemokine receptors CCR1 and CCR5. These G protein coupled receptors are both activated by a relatively large number of chemokines, most of which overlap. While most of the drugs for CCR1 have been assessed in the context of autoimmune diseases like multiple sclerosis and rheumatoid arthritis, and those for CCR5 were examined for HIV-infection, we review the role of these receptors in relation to cancer. Recently introduced pharmacophores that serve as agonists or antagonists for the receptors are presented. Efforts to exploit polypharmacology approaches using promiscuous compounds that target more than one receptor are also considered.
25141938 Roles of secreted phospholipases Aâ‚‚ in the mammalian immune system. 2014 Secreted phospholipase A2 (sPLA2) molecules constitute a family of proteins that are involved functionally in many biological processes. In particular, they participate in diverse pathophysiological settings as enzymes that release free fatty acids and lysophospholipids from phospholipids in biological membranes, or as ligands for various cellular receptors. In this review the confirmed or expected functions of sPLA2s in the mammalian immune system are surveyed. Some of the twelve mammalian sPLA2 molecules constitute part of the so-called innate immune system by virtue of their antibacterial, antiviral and antifungal activities. They are also involved in acute inflammation, a protective reaction of the body to infection or injury. The acute inflammation sometimes escapes regulation, becomes chronic and can evolve into a severe pathology. One or more types of sPLA2 are involved in asthma, rheumatoid arthritis, sepsis, atherosclerosis, myocardial infarction, Crohn's disease, ulcerative colitis and cancer. sPLA2s are thus important therapeutic targets as well as biotherapeutic molecules. Improving the selectivity of inhibitors of sPLA2s to be able to target a particular sPLA2 could therefore be one of the most important tasks for future research.
25048420 Association between indices of clinically-defined periodontitis and self-reported history 2016 Feb AIM: The aim of the current research was to investigate whether possible associations exist between indices of clinically-defined periodontitis and several systemic medical conditions in outpatients referred to a special hospital clinic. METHODS: The study sample consisted of 3360 outpatients aged 45-65 years. Data were collected by means of an oral clinical examination and a self-administered questionnaire. Statistical analysis of the questionnaire items was done with Fisher's exact test and the logistic regression model to assess possible associations between systemic medical conditions as independent variables, and the relative frequency of periodontal pockets ≥5 mm and clinical attachment loss (CAL) of ≥6 mm as dependent variables. RESULTS: The depth of periodontal pockets was significantly associated with male sex, the presence of vascular disease, hypertension, stroke, heart attack, diabetes mellitus, other endocrine diseases, thyroid disease, respiratory allergies, and rheumatoid arthritis. CAL was significantly associated with the mentioned conditions, and also infective endocarditis and chronic obstructive pulmonary disease, but not other endocrine and thyroid disease. CONCLUSIONS: The findings confirm the results from previous investigations in which a number of systemic medical conditions were significantly associated with probing pocket depth and/or CAL.
25012234 A high copy number of FCGR3B is associated with psoriasis vulgaris in Han Chinese. 2014 BACKGROUND: Copy number variations of FCGR3B are associated with several immune related diseases such as systemic lupus erythematosus, rheumatoid arthritis and primary Sjögren's syndrome. Little is known about the association between FCGR3B copy number variants and psoriasis. OBJECTIVE: To investigate whether FCGR3B copy number variants are associated with susceptibility to psoriasis vulgaris in the Chinese Han population. METHODS: 343 psoriasis vulgaris patients and 574 healthy individuals were recruited as cases and controls. TaqMan® Copy Number Assays were performed to quantify the copy numbers in the FCGR3B locus. CopyCaller v1.0 software and R (version 2.15.3) were used to do the subsequent statistical analysis. RESULTS: A significant association between psoriasis vulgaris and a high copy number (>2) of FCGR3B was observed (odds ratio = 1.63, 95% confidence interval 1.09-2.45, p < 0.02). However, the low copy number of FCGR3B was not significantly associated with psoriasis vulgaris. CONCLUSION: A high copy number of FCGR3B is associated with psoriasis vulgaris in Han Chinese.
24980140 TREG-cell therapies for autoimmune rheumatic diseases. 2014 Sep Naturally occurring Foxp3(+)CD25(+)CD4(+) regulatory T (TREG) cells maintain immunological self-tolerance and prevent a variety of autoimmune diseases, including rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. In animal models of rheumatic disease, autoimmune responses can be controlled by re-establishing the T-cell balance in favour of TREG cells. Here we discuss three potential strategies for the clinical use of TREG cells to treat autoimmune rheumatic disease: expansion of self-antigen-specific natural TREG cells in vivo; propagation of antigen-specific natural TREG cells ex vivo, by in vitro antigenic stimulation, and subsequent transfer back into the host; or conversion of antigen-specific conventional T cells into TREG cells in vivo or ex vivo. These strategies require depletion of the effector T cells that mediate autoimmunity before initiating TREG-cell-based therapies. Immunotherapies that target TREG cells, and the balance of TREG cells and autoreactive T cells, are therefore an important modality for the treatment of autoimmune rheumatic disease.
24964572 Allium sativum: facts and myths regarding human health. 2014 Garlic (Allium sativum L. fam. Alliaceae) is one of the most researched and best-selling herbal products on the market. For centuries it was used as a traditional remedy for most health-related disorders. Also, it is widely used as a food ingredient--spice and aphrodisiac. Garlic's properties result from a combination of variety biologically active substances which all together are responsible for its curative effect. The compounds contained in garlic synergistically influence each other so that they can have different effects. The active ingredients of garlic include enzymes (e.g. alliinase), sulfur-containing compounds such as alliin and compounds produced enzymatically from alliin (e.g. allicin). There is a lot of variation among garlic products sold for medicinal purposes. The concentration of Allicin (main active ingredient) and the source of garlic's distinctive odor depend on processing method. Allicin is unstable, and changes into a different chemicals rather quickly. It's documented that products obtained even without allicin such as aged garlic extract (AGE), have a clear and significant biological effect in immune system improvement, treatment of cardiovascular diseases, cancer, liver and other areas. Some products have a coating (enteric coating) to protect them against attack by stomach acids. Clinically, garlic has been evaluated for a number of purposes, including treatment of hypertension, hypercholesterolemia, diabetes, rheumatoid arthritis, cold or the prevention of atherosclerosis and the development of tumors. Many available publications indicates possible antibacterial, anti-hypertensive and anti-thrombotic properties of garlic. Due to the chemical complexity of garlic and the use of different processing methods we obtain formulations with varying degrees of efficacy and safety.
24953716 The gut microbiome. 2014 Since the discovery and use of the microscope in the 17(th) century, we know that we host trillions of micro-organisms mostly in the form of bacteria indwelling the "barrier organs" skin, gut, and airways. They exert regulatory functions, are in a continuous dialogue with the intestinal epithelia, influence energy handling, produce nutrients, and may cause diabetes and obesity. The human microbiome has developed by modulating or avoiding inflammatory responses; the host senses bacterial presence through cell surface sensors (the Toll-like receptors) as well as by refining mucous barriers as passive defense mechanisms. The cell density and composition of the microbiome are variable and multifactored. The way of delivery establishes the type of initial flora; use of antibiotics is another factor; diet composition after weaning will shape the adult's microbiome composition, depending on the subject's life-style. Short-chain fatty acids participate in the favoring action exerted by microbiome in the pathogenesis of type-2 diabetes and obesity. Clinical observation has pinpointed a sharp rise of various dysimmune conditions in the last decades, including IBD and rheumatoid arthritis, changes that outweigh the input of simple heritability. It is nowadays proposed that the microbiome, incapable to keep up with the changes of our life-style and feeding sources in the past few decades might have contributed to these immune imbalances, finding itself inadequate to handle the changed gut environment. Another pathway to pathology is the rise of directly pathogenic phyla within a given microbiome: growth of adherent E. coli, of C. concisus, and of C. jejuni, might be examples of causes of local enteropathy, whereas the genus Prevotella copri is now suspected to be linked to rise of arthritic disorders. Inflammasomes are required to shape a non colitogenic flora. Treatment of IBD and infectious enteritides by the use of fecal transplant is warranted by this knowledge.
24939591 Production of anti TNF-α antibodies in eukaryotic cells using different combinations of v 2015 Oct Tumor necrosis factor-α (TNF-α) plays a key role in rheumatoid arthritis and some other autoimmune diseases. Therapy with anti-TNF-α recombinant antibodies (Ab) appears to be highly effective. Production of new hyper-producing eukaryotic cell lines can decrease the treatment cost, which currently is very high. However, due to the complexity of protein transcription, translation, processing, and secretion in mammalian cells, the stages at which antibody expression is affected are still poorly determined. The aim of this work was to compare the productivity of two cell lines developed in CHO DG44 cells, deficient in dihydrofolate reductase, transfected with vectors carrying either heavy (H) or light (L) chains of chimeric antibody under different combinations of selective elements. Both H and L chains were cloned either in pOptiVEC or pcDNA3.3 vectors and different combinations were used to produce HL and LH cell lines. We have shown that Ab production has been low and comparable between HL and LH cells until selection on methotrexate (MTX) when LH but not HL cells have responded with 3.5 times increased productivity. Flow cytometry analysis has demonstrated that intracellular concentration of full size Abs in LH cells was 5.6 times higher than in HL ones due to higher amount of H chain synthesis. No differences in viability between HL and LH cells have been found. We have concluded that the expression of H chain in the pOptiVEC vector, which is responsible for MTX resistance, has led to the suppression of H chain synthesis and limitation in full Ab assembly.
24938190 Physiopathology of pain in rheumatology. 2014 Jun 6 Pain is the main manifestation of many rheumatic diseases (be they overtly inflammatory such as rheumatoid arthritis or dysfunctional such as fibromyalgia) but, at least initially, the mechanisms involved in the genesis, amplification and chronicisation of the persistent pain characterising the various conditions can be very different. The main peripheral mechanism underlying acute nociceptive pain is a change in the activity of the nociceptors located in the affected anatomical structures (joints, tendons and ligaments), which makes them more sensitive to normally painful stimuli (hyperalgesia) or normally non-painful stimuli (allodynia). This physiopathological mechanism of peripheral sensitisation plays a primary role in rheumatic diseases characterised by acute inflammation, such as the arthritides due to microcrystals. In the case of chronic rheumatic diseases that do not regress spontaneously, functional and structural central nervous system changes cause a generalised reduction in the pain threshold that is not limited to the anatomical structures involved, thus leading to the appearance of hyperalgesia and allodynia in many, if not all body districts. This is the physiopathological basis of chronic, widespread musculoskeletal pain.
24899377 Inhibition of human pyridoxal kinase by 2-acetyl-4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)i 2015 Apr 2-Acetyl-4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)imidazole (THI) is observed as a minor contaminant in caramel food colourings (E 150c). Feeding experiments with rodents have revealed a significant lymphopenic effect that has been linked to the presence of THI in these food colourings. Pyridoxal kinase inhibition by THI has been suggested, but not demonstrated, as a mode of action as it leads to lowered levels of pyridoxal-5'-phosphate, which are known to cause lymphopenia. Recently, THI was also shown to inhibit sphingosine-1-phosphate lyase causing comparable immunosuppressive effects and derivatives of THI are being developed for the treatment of rheumatoid arthritis in humans. Interestingly, sphingosine-1-phosphate lyase activity depends on pyridoxal-5'-phosphate, which in turn is provided by pyridoxal kinase. This report shows that THI does inhibit pyridoxal kinase with competitive and mixed-type non-competitive behaviour towards its two substrates, pyridoxal and ATP, respectively. The corresponding inhibition constants are in the low millimolar range.