In this study, an elevated KFLC-index represented the most sensitive and specific quantitative diagnostic parameter for MS. As it is measured by automated, routinely available laboratory methods, KFLC quantitation can provide a rapid and reproduceable indication of intrathecal immunological processes supporting current MS diagnostic criteria.
The target range proposed by this explorative study may serve as an initial guidance for MPA monitoring in the context of further prospective controlled trials in patients with AID.
Abstract. Mycophenolate mofetil (MMF), being effectively used as immunosuppressant in transplant medicine, has recently attracted interest as therapeutic agent for autoimmune diseases (AID). For these patients, no pharmacokinetic (PK) data are available. This study is an investigation of single-dose concentration-time profiles of 1 g off MMF in 16 patients with AID, including 10 patients with ANCA-associated vasculitis and 6 patients with systemic lupus erythematosus, and compares them with profiles of 16 renal transplant recipients (RTX). Mycophenolic acid (MPA) blood levels were measured by both HPLC and EMIT, and MPA-glucuronide was determined by HPLC. In AID, mean MPA concentrations at 12 h were significantly higher compared with RTX (4.1 Ϯ 3.27 versus 1.8 Ϯ 1.15 mg/L; P ϭ 0.018), whereas peak concentrations were lower (P ϭ 0.017). However, mean MPA-AUC at 12 h as well as at 24 h were comparable between both groups. In contrast to RTX, there was an association in AID between MPA trough levels at 12 h and at 24 h with AUC 0-12 (P Ͻ 0.05 and P Ͻ 0.01). MPA trough concentrations at 24 h provided an estimation of AUC 0-24 h in both patient groups (P Ͻ 0.001 and P Ͻ 0.01; AID and RTX, respectively). Compared with RTX, MPA-PK seems to be less affected in AID by renal function. Inter-individual variability of PK parameters was high in both groups. These data indicate that there are differences of MPA-PK between RTX and AID. The use of therapeutic drug monitoring in patients with AID appears to be clinically practicable and may be valuable to optimize individual immunosuppressive therapy.The positive experience with mycophenolate mofetil (MMF) in the field of solid organ transplantation made this drug attractive for the treatment of several autoimmune diseases (1-4). Promising data derived from pilot studies suggests a therapeutic potential of MMF in the treatment of ANCA-associated small vessel vasculitis (ASVV) and systemic lupus erythematosus (SLE) (5,6). In a randomized trial from Hong Kong comparing MMF with cyclophosphamide in patients with diffuse proliferative lupus nephritis, remission and relapse rate were comparable in both groups, whereas MMF was better tolerated (7). Nevertheless, for these patients neither recommendations for optimal dosage of MMF nor data concerning drug exposure of MMF are available.In kidney transplant recipients, several studies have shown a relationship between pharmacokinetic (PK) parameters with efficacy and toxicity. While patients with a low area under the concentration-time curve (AUC) of the active metabolite mycophenolic acid (MPA) appear to be at high risk for experiencing graft rejection (8), a relationship between MPA-PK and adverse effects has been found (9). Higher dosages like 3 g/d were associated with an increased occurrence of adverse effects; therefore, MMF is usually administered at a fixed daily dose of 2 g/d divided into two applications (10). However, the considerable individual variability and changes over time of PK parameters of MPA (10,11) as well as drug ...
The aim of this study was to determine the performance of antibodies against mutated citrullinated vimentin (anti-MCV) in comparison with antibodies to cyclic citrullinated peptides (anti-CCP) in patients with rheumatoid arthritis (RA). Serum levels of anti-MCV and anti-CCP were determined in 193 patients with RA and 332 controls, and sensitivity and specificity were calculated. In a separate analysis of 86 patients, the anti-MCV levels were compared to disease activity. Sensitivity of anti-MCV versus anti-CCP was 71.5 and 69.4%, specificity was 81.3 and 97.6%, respectively. The ROC curves showed higher specificity and an advantage of anti-CCP. In seronegative RA patients the sensitivity of anti-MCV was superior over anti-CCP. Anti-MCV positivities also occurred in systemic lupus erythematosus and Sjoegren's syndrome. In a subgroup of 86 RA patients we found a significant correlation between anti-MCV and disease activity. Anti-MCV appears to be an important marker for the diagnosis of RA, and correlates also with disease activity.
To quantify osseous breakdown in multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), and benign osteoporosis, we measured urinary levels of pyridinium cross-links of collagen in 50 patients with newly diagnosed and untreated MM, 40 patients with MGUS, 40 untreated patients with osteoporotic vertebral fractures, and 64 healthy adults. Ion-paired, reverse-phase high-performance liquid chromatography (HPLC) was used to measure total urinary excretion of pyridinoline (h-PYD) and deoxypyridinoline (h-DPD). Urinary excretion of free immunoreactive deoxypyridinoline (i-DPD) was determined with an enzyme immunoassay. MM patients had significantly (P < .0001) higher levels of h-PYD, h-DPD, and i-DPD than the healthy adults, patients with MGUS, or patients with osteoporosis. The MGUS and osteoporosis groups presented with elevated (P < .05) levels of urinary pyridinium cross-links when compared with healthy controls. In 20 MM patients who subsequently received chemotherapy, the percent changes in i-DPD did not correlate with the changes in the monoclonal protein. In one of three patients experiencing a transition of initial MGUS into stage I MM, i-DPD increased above the upper limit of the normal range. In 13 patients with stable MGUS, i-DPD remained normal in repeated measurements. Based on the upper limits of the normal range, the sensitivity of urinary pyridinium cross-links in stage I and II MM was low (<50%), but it was between 78% (h-DPD) and 93% (i-DPD) in stage III MM. Specificity in patients with MGUS was between 87% (h-PYD) and 97% (h-DPD). In conclusion, determining the urinary excretion of pyridinium cross-links seems to be a promising noninvasive and thus easily repeatable method for evaluating the actual degree of osseous breakdown. Although measurement of pyridinium cross-link levels is not useful in discriminating patients with MGUS from early-stage myeloma patients, determination of i-DPD levels may contribute importantly to clinical guidance, since increased i-DPD levels seem to identify patients who are particularly likely to benefit from osteoclast-inhibiting drugs such as bisphosphonates. The fact that in a number of patients paraprotein concentrations and i-DPD levels did not change in parallel but instead diverged strongly after chemotherapy might explain the observation that bone lesions sometimes progress even in patients who achieve complete remission.
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