Anti-C1q antibodies in patients with systemic lupus erythematosus treated by rituximab


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AIM: To determine the time course of changes in the blood levels of antibodies (Ab) to complement component C1q (a-C1q) in patients with systemic lupus erythematosus (SLE) during rituximab (RTM) therapy and the association with organ injuries in SLE/MATERIAL AND METHODS: The study involved 41 patients (3 men and 38 women; their median age was 27.5 (range 22-36) years) with definite SLE. Their blood a-C1q levels were determined by enzyme immunoassay. The levels and detection rates of a-C1q were estimated in relation to organ injuries, the time course of RTM therapy-induced changes in a-C1q levels were determined. High-positive (>30 U/ml), low-positive (10-30 U/ml), and negative (≤10 U/ml) a-C1q levels were found/RESULTS: A-C1q was detected in 19 (46.3%) patients with different clinical manifestations of SLE. The patients with renal diseases had high-positive levels of a-C1q statistically significantly more frequently than those without renal involvement (p=0.04). Low-positive and negative a-C1q levels were found in 15 of 16 without nephritis. There was a statistically significant positive correlation of the concentration of a-Clq with Ab to double-stranded DNA (a-dsDNA), Ab to nucleosomes, the SLE Disease Activity Index 2000 (SLEDAI-2K), erythrocyturia, hematuria and a negative correlation between a-C1q and complement components C3 and C4. Just after one month of RTM therapy, the patients with nephritis were observed to have a statistically significant decrease in the levels of a-C1q (p=0.002), which persisted 1 year after the treatment (p=0.006). Nineteen patients with the higher baseline concentrations of a-C1q after RTM treatment showed a statistically significant decrease in the levels of a-C1q at 1-, 3-, 6-, and 12-month follow-up (p=0.016, 0.02, 0.035, and 0.04, respectively) which was accompanied by the decreased SLEDAI-2K (p<0.00004 at 1-, 3-, 6-, and 12-month follow-up)/CONCLUSION: The high levels of a-C1q were found statistically significantly more often in the patients with lupus nephritis than in those with SLE without renal involvement. The level of a-C1q statistically significantly reduced after RTM therapy and remained within the normal range during a year.

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Антитела к компоненту С1q комплемента у больных системной красной волчанкой на фоне лечения ритуксимабом. - Резюме. Цель исследования. Динамическая оценка уровней антител (АТ) к компоненту С1q комплемента (а-С1q) в крови у больных системной красной волчанкой (СКВ) на фоне терапии ритуксимабом (РТМ) и связи с поражением органов при системной красной волчанке (СКВ). Материалы и методы. Наблюдали 41 пациента с достоверной СКВ: 3 мужчины и 38 женщин; средний возраст 27,5 (22; 36) года. Уровень а-С1q в крови определяли с помощью иммуноферментного анализа. Оценивали уровни и частоту обнаружения а-С1q в зависимости от поражения органов, динамику на фоне терапии РТМ. Выделены высоко позитивные (>30 ед./мл), низко позитивные (10-30 ед./мл) и негативные (≤10 ед./мл) уровни а-С1q. Результаты. а-С1q обнаружены у 19 (46,3%) больных с различными клиническими проявлениями СКВ. У больных с поражением почек высоко позитивные уровни а-С1q встречались статистически значимо чаще, чем у больных без вовлечения почек (р=0,04). У 15 из 16 больных без нефрита выявлялись негативные и низко позитивные уровни а-С1q. Выявлены статистически значимая корреляция концентраций а-С1q c АТ к двуспиральной ДНК (а-дсДНК), АТ к нуклеосомам, индексом активности СКВ по SLEDAI2K, уровнем эритроцитурии и отрицательная корреляция с концентрацией компонентов С3, С4 комплемента. В группе больных с нефритом уже через 1 мес после терапии РТМ отмечалось статистически значимое снижение уровней а-С1q (р=0,002), которые сохранялись через 1 год после проведения терапии (р=0,006). У 19 больных с изначально повышенными концентрациями а-С1q в результате лечения РТМ наблюдалось статистически значимое снижение уровней а-С1q через 1, 3, 6 и 12 мес наблюдения (р=0,016, 0,02, 0,035 и 0,04 соответственно), которое сопровождалось снижением индекса активности СКВ по SLEDAI2K (p<0,00004) через 1, 3, 6 и 12 мес наблюдения. Заключение. Высокие уровни а-С1q у больных с волчаночным нефритом выявляются статистически значимо чаще, чем у больных СКВ без поражения почек. Уровень а-C1q статистически значимо снижается после проведения терапии РТМ и остается в пределах нормы в течение года.
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