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Increased serum PAD4 and RF in lung cancer is not associated with anti CCP antibody production
  1. Zsuzsanna Baka1,
  2. Peter Barta2,
  3. György Losonczy2,
  4. Tibor Krenács3,
  5. Judit Pápay3,
  6. Eszter Szarka4,
  7. Gabriella Sármay4,
  8. Anna Magyar5,
  9. Edit Buzás1,
  10. András Falus1,
  11. György Nagy1,6
  1. 1Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary
  2. 2Department of Pulmonology, Semmelweis University, Budapest, Hungary
  3. 3Department of Pathology, Semmelweis University, Budapest, Hungary
  4. 4Department of Immunology, Eötvös Loránd University, Budapest, Hungary
  5. 5HAS-ELTE Research Group of Peptide Chemistry, Budapest, Hungary
  6. 6Department of Rheumatology, Semmelweis University, Budapest, Hungary


Background Rheumatoid arthritis (RA) is characterised by anticitrullinated protein antibodies (ACPAs), produced against citrullinated proteins. In the pathogenesis of the disease the interaction of environment and genetics have a role as smoking is an important risk factor for the development of ACPA positive RA, especially in shared epitope carriers. However, the link among smoking, citrullination, catalysed by peptidyl arginine deiminases (PADs), and ACPAs has not yet been elucidated. Thus, we searched for a model without polyarthritis where there is increased cell death allowing the formation of autoantibodies.

Objectives We proposed that lung cancer might be a good candidate supported by the following considerations: smoking plays a role in its pathogenesis; the disease is often accompanied by paraneoplastic syndrome; smoking increases citrullination in the lung; several malignant tumour tissues are associated with increased citrullination; RA synovium and lung cancer tissue have similarities.

Patients and methods Serum PAD4, rheumatoid factor (RF) and ACPA levels were measured in 42 lung cancer patients and 67 non-tumourous pulmonary patients and healthy controls. All parameters were compared according to smoking history. None of the patients had polyarthritis or autoimmune disease.

Results Abnormal PAD4 and RF levels were frequently found in smoker lung cancer patients, compared to non-smokers. Two out of 30 smoker lung cancer patients had high anti-CCP levels. Smoking intensity (packyears) was significantly higher among smoker lung cancer patients, compared to healthy smokers, however, did not correlate to the measured serum parameters.

Conclusions smoking might influence PAD4 levels and RF production. High serum PAD4 and RF levels together with smoking are not sufficient for the formation of ACPAs and autoimmunity.

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