Anti-TNFα therapy in rheumatoid arthritis and autoimmunity

Abstract

The aim of the study was to evaluate a panel of autoantibodies in patients affected by rheumatoid arthritis (RA) treated with anti-TNFalpha blockers, and to consider a different autoantibody induction effect by infliximab and etanercept; and in addition to evaluate in these cases a relationship between antinuclear antibody (ANA) titre and both C-reactive protein (CRP) and Blys levels. Fifty-four patients (8 men, 46 women, mean age 51.4 years, mean duration of disease 13.6 years) affected by refractory RA were treated with anti-TNFalpha blockers for 12 consecutive months; 43 patients were given infliximab and 11 etanercept. At baseline and every 4 months a panel of autoantibodies consisting of rheumatoid factor, antinuclear, anti-double-stranded DNA, anti-ENA, anti-mitochondrial, anti-thyroid and anti-neutrophil cytoplasmic antibodies (ANCA) was tested. At the same time CRP level was measured. Blys level was determined at baseline and after 1 year in five cases that developed a strong positivity for ANA during infliximab therapy. In 41 cases (95.3%) treated with infliximab, ANA were detected on at least one occasion, and in almost half of these cases the titre was very high, equal to or higher than 1:1.280. On the other hand, patients treated with etanercept presented ANA positivity in a lower percentage of cases and at a low titre. No correlation was found between ANA titre and CRP level; Blys level did not present a constant trend in patients who developed a very high positivity for ANA. Anti-double-stranded DNA, anti-thyroid or ANCA were found only in a few patients, in the absence of a clinical picture indicative of systemic lupus erythematosus, autoimmune thyroiditis or ANCA-associated vasculitis. A different incidence of ANA positivity was found in infliximab- and etanercept-treated RA patients; this finding might be due to the partially different method of inhibition of TNFalpha between the two drugs. Both CRP and Blys do not seem to participate in this phenomenon. Other autoantibodies were detected in a few patients, but no case of onset of new autoimmune disorders was observed.

Production of Antibodies in Hybridoma and Non-hybridoma Cell Lines

“…Many of the side effects occur as a result of suppression of the immune system and result in severe infections due to bacterial, mycobacterial, invasive fungal, viral, protozoal, or other opportunistic pathogens (Caramaschi et al 2006). Among opportunistic infections tuberculosis, candidiasis, and pneumocystosis have been reported.…”

Anti-TNF tedavilerin tetiklediği otoimmünite

“…Bu çalışmada ANA pozitifliği infliximab sonrası %24'ten %69'a çıkmıştır. Daha sonra yapılan çalışmalarda da RA'lı ve SPA'lı hastalarda anti-TNF ilişkili ANA pozitifliği olduğunu ve ANA pozitifliğinin her iki hasta grubunda da infliximab kullanımına bağlı olduğunu göstermiştir (15)(16)(17).…”

Tumor necrosis factor α antagonists in the treatment of the patients with rheumatoid arthritis

“…Leczenie ETA indukuje w osoczu pacjentów chorych na RZS powstawanie autoprzeciwciał, zwłaszcza przeciwciał przeciwjądrowych (anti-nuclear antibodies -ANA), przeciwciał przeciwko dwuniciowemu DNA (anty-dsDNA) oraz antykardiolipinowych (aCL) [8,12,18,26]. Wiadomo także, iż obecność leku w organizmie chorych prowadzi do generowania przeciwciał przeciwko samemu ETA (human anti-human antibodies -HAHA), jednakże zjawisko to nie powoduje pogorszenia aktywności ETA [12,23,27].…”

“…Do najczęstszych działań niepożądanych ETA należą reakcje w miejscu wstrzyknięcia, takie jak ból, obrzęk, świąd, rumień czy krwawienie. Ponadto u chorych leczonych ETA może wystąpić reaktywacja utajonej gruźlicy czy wirusowego zapalenia wątroby typu B (hepatitis B virus -HBV) [4,16,18,[24][25][26]. Z doniesień literaturowych wynika jednak, że odsetek chorych, u których w wyniku leczenia biologicznego doszło do uaktywnienia się gruźlicy, jest zdecydowanie niższy przy zastosowaniu ETA niż w przypadku leczenia IFX czy ADA [18,19,25].…”

“…Infliksymab ma większą zdolność do indukowania autoprzeciwciał niż ETA czy ADA, jednak powstałe przeciwciała ANA i anty-DNA należące do klasy IgA, IgM oraz IgG zanikają wkrótce po odstawieniu leku [8,12,18,23,26]. Obecność IFX w organizmie stymuluje również powstawanie przeciwciał skierowanych przeciwko zmiennemu regionowi mysiej immunoglobuliny G (human anti-mouse antibodies -HAMA) obecnemu w strukturze omawianego leku.…”