Daratumumab Interference in Pretransfusion Testing Is Overcome by Addition of Daratumumab Fab Fragments to Patients' Plasma.

BACKGROUND: Daratumumab (DARA), an IgG1κ human monoclonal anti-CD38 antibody, is used for the treatment of refractory myeloma for example. Binding of DARA to CD38 on red blood cells (RBCs), however, leads to panagglutination in indirect antiglobulin testing and possibly masks clinically relevant alloantibodies. Dithiothreitol eliminates panreactivity by destroying CD38 but has the drawback of modifying certain blood group antigens and, thereby, impairs the detection of alloantibodies. METHODS: DARA was digested for 16 h at 37°C using immobilized papain in a spin column, centrifuged, and washed, and the DARA-Fab fragments in pooled flow-throughs were stored at -20°C. DARA-Fab and test cells (ID-DiaCell I-II-III or ID-DiaPanel; BioRad) were incubated with human plasma spiked with DARA (plasma concentration up to 1,000 mg/L) or plasma from patients under DARA therapy at 37°C for 15 min. Thereafter, ID-Cards LISS/Coombs were used. RESULTS: Immunofixation electrophoresis showed complete fragmentation of DARA into Fc and Fab fragments by papain proteolysis. DARA-Fab efficiently prevented RBC agglutination by patients' plasma and by plasma spiked with DARA. Moreover, DARA-Fab did not interfere with the detection of alloantibodies. CONCLUSION: We present a quite easy, reproducible, and cost-effective method for DARA-Fab fragment preparation. Blocking CD38 epitopes with DARA-Fab easily overcomes DARA interference in pretransfusion testing without affecting alloantibody detection.

Serum hyaluronic acid levels are elevated in arthritis patients, but normal and not associated with clinical data in patients with fibromyalgia syndrome.

BACKGROUND: Fibromyalgia syndrome (FM) is a disease with widespread chronic pain and many nonspecific symptoms. Hyaluronic acid (HA) is a disputed marker for the diagnosis of FM. The aim of the study is to clarify the discrepant results reported so far. METHODS: Serum concentrations of HA were measured with a radiometric assay (Pharmacia & Upjohn, Sweden) in 41 patients with FM (38 females), 48 with arthritis (35 females) and 31 control subjects (28 females). Correlations of HA levels with clinical parameters (duration of disease, age, gender, medication) and scores of disease severity (e.g. depression and pain) were calculated. If appropriate, partial correlations and analysis of covariance adjusted for confounding variables (e.g. age) were used. RESULTS: HA levels were confirmed to be age-related in the whole study group (r(s) = 0.54; P < 0.001) and each subgroup. Association between HA levels and gender, drug therapy, clinical or psychometric data could not be demonstrated in patients suffering from FM. Analyzing all study participants, HA levels were correlated with the pain disability index (PDI) (r(tau) = 0.27; P < 0.02) and, in arthritis patients only, with duration of disease (r(tau) = 0.82; P < 0.001). Moreover, analysis of covariance revealed that patients with FM had normal HA values as compared with control subjects and only patients with arthritis had significantly higher levels than both other groups. CONCLUSIONS: The present study with a quite large cohort including patients with arthritis and FM demonstrates that serum levels of HA in FM are neither elevated nor associated with any relevant clinical data of this disease and, therefore, have no diagnostic or prognostic value in Germans.

Cholesterol levels linked to abnormal plasma thiol concentrations and thiol/disulfide redox status in hyperlipidemic subjects.

Treatment of hyperlipidemic patients with the thiol compound N-acetylcysteine (NAC) was previously shown to cause a significant dose-related increase in the high-density lipoprotein (HDL)-cholesterol serum level, suggesting the possibility that its disease-related decrease may result from a diminished thiol concentration and/or thiol/disulfide redox status (REDST) in the plasma. We therefore investigated plasma thiol levels and REDST in normo-/hyperlipidemic subjects with and without coronary heart disease (CHD). The thiol level, REDST, and amino acid concentrations in the plasma and intracellular REDST of peripheral blood mononuclear cells (PBMC) have been determined in 62 normo- and hyperlipidemic subjects. Thirty-three of these subjects underwent coronary angiography, because of clinical symptoms of CHD. All groups of hyperlipidemic patients under test and those normolipidemic individuals with documented coronary stenoses showed a marked decrease in plasma thiol concentrations, plasma and intracellular REDST of PBMCs, and a marked increase in plasma taurine levels. Individual plasma thiol concentrations and plasma REDST were strongly negatively correlated with the serum LDL-cholesterol and positively correlated with the serum HDL-cholesterol level. Together with the earlier report about the effect of NAC on the HDL-cholesterol serum level, our findings suggest strongly that lower HDL-cholesterol serum levels may result from a decrease in plasma thiol level and/or REDST possibly through an excessive cysteine catabolism into taurine.

Cerebrospinal fluid tau levels in Alzheimer's disease are elevated when compared with vascular dementia but do not correlate with measures of cerebral atrophy.

Increased tau levels are a well-established finding in Alzheimer's disease (AD). In contrast, the potential value of tau levels in the differential diagnosis of AD, vascular dementia (VD) and major depression warrants further investigation. The potential impact of psychotropic medication also needs to be established. We investigated cerebrospinal fluid (CSF) tau protein concentrations in 88 patients with AD, 23 patients with VD, 25 patients with major depression and 17 age-paralleled controls without cognitive impairment with respect to important clinical variables, type and dosage of psychotropic medication and cerebral changes as assessed by magnetic resonance imaging (MRI). The AD patients showed significantly elevated tau levels compared with patients with VD or major depression and controls. Tau levels obtained in the VD group were intermediate, with significant differences from both AD patients and patients with major depression and controls. Within the AD group, no significant correlation between tau levels, severity of dementia, age, duration of disease, type and dosage of psychotropic medication or MRI volumetric changes arose. A subgroup of AD patients without increased tau levels was characterized by a significantly larger percentage of patients with presenile onset.