P001 What is the role of antidrug antibody and drug level testing in patients treated with infliximab and adalimumab?

Background/Aims Approximately 30-40% of rheumatology patients fail to respond to first-line biologics. Secondary inefficacy is mediated by immune complex formation between biologic agents and anti-drug antibodies. Anti-drug antibody testing has been undertaken at Sheffield Teaching Hospitals since October 2015. However, there are currently no national guidelines or consensus on what levels of anti-drug antibodies are clinically significant or what changes to therapy are suggested as a consequence of these tests. We aimed to review the reasons for and outcomes of anti-drug antibody levels tested at STH in patients on Adalimumab or Infliximab. Methods Retrospective review of records of all Rheumatology patients having antidrug antibody levels tested October 2015 - April 2019. Results 237 patients were included in this analysis. The mean age of patients was 48 years. 43% were male. The most common reasons for testing antibody levels were clinical evidence of a flare in disease (n = 92) and patient reported worsening of symptoms (n = 88). 66% (n = 157) of antibody levels tested were negative, 21% (n = 49) of tests were strongly positive (antibody titre >50). Serum drug concentrations were subtherapeutic in 20 % (n = 47), therapeutic in 22% (n = 51) and supratherapeutic in 38% (n = 91). In 51% of patients (n = 119) the current treatment regime was continued. However, 38% (n = 90) changed biologics, and dosing schedule was changed in 2% (n = 6). Antibody titres were more likely to be strongly positive in patients who had clinically active disease compared to those who had symptoms but no clinical evidence of disease (30% vs 10% p = 0.009). Those with strongly positive antibodies were more likely to switch biologics than those with normal antibodies (84% vs 28%, p = 0.01). Patients with clinically active disease but normal antibodies and drug levels were more likely to switch biologics than patients with no evidence of active disease but positive antibodies (p = 0.03). Underlying diagnosis (p = 0.23) or concomitant DMARD use (p = 0.92) were not associated with positive autoantibodies. Of the 47 patients with subtherapeutic drug levels, 61% (n = 29) had strongly positive anti-drug antibodies and 73% (n = 34) subsequently switched biologics. 49% (n = 111) of patients had both therapeutic drug levels and normal antibodies. Of these, 22% (n = 25) switched biologics. Of the 25 patients that switched biologics 24% (n = 6) did not have evidence of active disease and 76% (n = 19) had active disease. Conclusion 33% of patients had positive autoantibodies. 39% of patients switched biologics following testing. There was no protective effect of DMARDs identified. Patients with active disease were more likely to have positive antibodies and to switch biologics than those with no clinical evidence of disease. 25% of patients had subtherapeutic drug levels. However, only 2% of patients had a dose schedule adjustment. Therefore, dosing schedule alterations could be considered in these patients prior to escalating to a more expensive biologic. Disclosure M. Cox: None. R. Smith: None. G. Wild: None. L. Dunkley: None.

Screening for celiac disease among patients of the gastroenterological profile

Aim. To determine the frequency of celiac disease (CD) among gastroenterological patients and criteria for its active detection. Materials and methods. 1.358 patients referred for gastroenterologist consultation from 2016 to 2019 was conducted, of which 140 had CD (339 males 24.9%; 1019 females 75.1%). The average age was 40.415.4 (1886 years). All patients were determined anti-TTG IgA, IgG, and analyzed the clinical symptoms and analysis. The results were subjected to statistical processing Statistica 13.3 (StatSoft Inc., USA). Results. In patients without CD (1218 people), high level of anti-TTG IgA and IgG was observed in 59 (4.8%), an increase in anti-TTG IgA in 54 (4.4%), and anti-TTG IgG in 38 patients (3.1%). The CD diagnosis confirmed in 51 patients (4.2%). The main symptoms were diarrhea (88%), abdominal pain (60.7%), bloating (73.8%), nausea (40.3%), weight loss (44.3%). Anemia was determined in 31.6%, serum iron 33%, hypoproteinemia 12.6%, hypoalbuminemia 12%, hypokalemia 5.48%, hypocalcemia 21.9%. An increase in the level of AST 14.5%, ALT 14.6%. Comparative analysis showed that in the group with newly detected CD, anemia, malabsorption syndrome, increase AST, ALT were significantly more frequent than in patients with normal antibodies, which confirms the need to detect CD among patients with these laboratory abnormalities. Conclusion. The incidence of CD among patients with a gastroenterological symptoms was 4.2%. Analysis of clinical and laboratory data has shown that a comprehensive analysis of clinical symptoms and laboratory indicators at the stage of primary treatment will allow timely identification of CD patients and prescribe GFD.

Effect of the duration of feeding iodine-containing preparation to pregnant cows on the immunobiochemical status of newborn calves

Амурская область принадлежит к биогеохимической провинции с низким содержанием йода. Введение глубокостельным коровам йодсодержащего препарата «Вангцейод» в профилактической дозе в течение 60 дней сопровождалось изменениями в клеточной системе иммунитета полученных от них телят, а именно: оказало стимулирующее влияние на фагоцитарную активность нейтрофилов, их агрессивность и поглотительную способность. У телят опытной группы показатели гуморального звена защиты были выше, чем в контроле, что подтверждалось более высоким содержанием иммуноглобулинов (на 13 %), циркулирующих иммунных комплексов (на 60,7 %), титра нормальных антител (на 68,4 %) и повышением активности лизоцима на 22,6 %. Применение йодсодержащего препарата в зоне йодной недостаточности нормализует обменные процессы и усиливает иммунобиохимическую защиту организма животных, что позволяет повысить продуктивность коров и сохранность новорожденных телят. The Amur Region belongs to a biogeochemical province with low iodine content. The introduction of the iodine-containing drug “Vangzeyod” to pregnant cows in a preventive dose for 60 days was accompanied by changes in the cellular system of immunity of calves received from them, namely: had a stimulating effect on the phagocytic activity of neutrophils, their aggressiveness and absorption capacity. In the experimental group of calves, the indicators of humoral protection were higher than in the control group, that was confirmed by a higher content of immunoglobulins (by 13 %), circulating immune complexes (by 60.7 %), the titer of normal antibodies (by 68.4 %), and an increased activity of lysozyme by 22.6 %. The use of an iodine-containing drug in the zone of iodine deficiency normalizes metabolic processes and strengthens the immunobiochemical protection of the animal body, which allows increasing the productivity of cows and the safety of newborn calves.

Association between hypogonadism and reproductive tissue steroid-producing cells antibody in men with positive MAR test IgG and diabetes mellitus type 1

BACKGROUND: Autoimmune hypogonadism is frequently taped in men with positive direct mixed agglutination reaction antisperm antibodies IgG test (MAR test IgG). AIMS: Тo assess pathogenetic factor of autoimmune hypogonadism in men with positive MAR test IgG and diabetes mellitus type 1 (DM1). MATERIALS AND METHODS: A retrospective study included 97 patients with positive direct MAR test IgG: 30 men with DM1 and 67 without DM. Assessment included testosterone level and titer of summary reproductive tissue steroid-producing cells antibody (LCA). Statistically significant differences were p0,05. RESULTS: 43% of men with DM1 have abnormal LCA titer and it was significantly higher than in patients without DM 21%. In both groups testosterone level was significantly lower in men with abnormal LCA titer than in patients with normal antibodies titer. Frequency of hypogonadism in men with abnormal LCA titer was significantly higher than in patients with normal antibodies titer also in both groups. There were no significantly differences of MAR test IgG in patients with normal and abnormal LCA titer. CONCLUSIONS: Autoimmune hypogonadism is a common complication in men with DM1 and positive MAR test IgG and its strongly associated with high titer of summary reproductive tissue steroid-producing cells antibody.

Clinical and Immunological Analysis of Cutaneous Leishmaniasis before and after Different Treatments

Amastigotes fromL. (L.)amazonensis(La),L. (L.)venezuelensis(Lv),L. (V.)brasiliensis(Lb), andL. (L.)chagasi(Lch) were cultured in a free cells liquid culture medium. Patients (n=87) from a cutaneous leishmaniasis (CL) hyperendemic region receiving different treatments were followed up from January 1994 to August 2000. Time for remission of lesions were spontaneous remission (SR) 7 weeks; Glucantime (Glu) chemotherapy 9 weeks; immunotherapy with La, Lv, Lb, and Lch amastigotes Tosyl-Lysil Chloromethyl-ketone (TLCK) treated and Nonidet P-40(NP-40) extracted (VT) 7 weeks. Delayed type hypersensitivity (DTH) response with leishmanine intradermic reaction (IDR) was higher in CL patients than healthy controls (P<0.05) and increased in active secondary versus primary infection (P<0.001) with diagnostic value 1.74 for active infection and 1.81 postclinical remission. Antibodies to amastigotes characterized by Enzyme Linked Immunosorbent Assay (ELISA) decreased in sera postclinical remission versus active infections (P<0.001), with a diagnostic value from 1.50 to 1.84. Immunoblottings antigenic bands frequency as well as Integral Optical Density (IOD) Area Densitometry decreased with sera from SR, after Glu or VT treatments in CL volunteers. Intracellular parasitism is due to normal antibodies recognizing parasite antigens after inoculation by vector. VT vaccine induced mainly cellular immunity, for remission of lesions and protection from CL infection.

Thrombocytopenia after second exposure to abciximab is caused by antibodies that recognize abciximab-coated platelets

Thrombocytopenia, often severe, occurs in 1% to 2% of patients given the fibrinogen receptor antagonist abciximab, a chimeric Fab fragment containing murine specificity-determining and human framework sequences. The cause of this complication has not yet been defined. Studies of 9 patients who developed profound thrombocytopenia (platelets &lt;10 × 109/L [10 000/μL]) within a few hours of being given abciximab a second time showed that each had a strong immunoglobulin G (IgG) antibody that recognized platelets sensitized with abciximab. Five patients also had IgM antibodies. IgG antibodies reactive with abciximab-coated platelets were also found in 77 (74%) of 104 healthy subjects. However, the patient antibodies could be distinguished from “normal” ones in 2 ways: (1) only the patient antibodies reacted preferentially with platelets sensitized with the intact monoclonal antibody 7E3 from which the murine sequences in abciximab are derived; and (2) the “normal” antibodies could be inhibited by Fab fragments derived from normal human IgG, whereas the patient antibodies were relatively resistant to this treatment. The findings suggest that antibodies from the patients are specific for murine sequences in abciximab and are capable of causing life-threatening thrombocytopenia upon injection of this drug. The antibodies commonly found in healthy subjects are specific for the papain cleavage site of any Fab fragments and, although they react with abciximab-coated platelets, appear not to cause significant thrombocytopenia. It may be possible to identify patients at risk for developing thrombocytopenia if given abciximab by screening for antibodies that recognize 7E3-coated platelets.