The Role Of TNF-NF?B Pathway,JAK-STAT Pathway And IFN-? In Pathogenesis Of Erythema Nodosum

1.Background and ObjectiveErythema nodosum(EN)is the most common type of panniculitis mainly involving the septa between subcutaneous adipose lobules without vasculitis.It may have many aetiological factors,but its exact pathogenesis is still not clear.Recent study shows that tumor necrosis factor-nuclear factor-?B(TNF-NF?b)signal pathway and Janus kinase-signal transducer and activator of transcription(JAK-STAT)signal pathway are significantly activated in inflammatory bowel disease-related EN lesions.However,Interferon-y(IFN-y),which plays an important role in immune defense by activating multiple signal pathway,has not been proved to be related to EN pathogenesis.The purpose of this study is to investigate the expression patterns of TNF-?,NF?B,STAT1,STAT3 and IFN-y in cutaneous lesions of EN by immunohistochemistry staining.2.PatientsThe study group(23 case)consisted of patients with EN who received skin biopsy in Dermatology Department of Peking Union Medical College Hospital from May 2018 to December 2019.Gender,age,results of preoperative laboratory examinations,sites of biopsy and pathological diagnosis were recorded.The normal control(1 case)was selected from patients who received pigmented nevus resection in Dermatology Department of Peking Union Medical College Hospital.3.MethodImmunohistochemistry was carried out for the TNF-?,NF?B,STAT1,STAT3 and IFN-y on the sectioned paraffin embedded skin tissue.Semi-quantitative score ranged from negative(-)to strongly positive(+++)according to staining color and percent of positive cells as well as average optical density(AOD)measured by ImageJ were used for evaluation of immunostaining in adipose tissue.4.Resultsa)The study group consisted 23 patients with EN,with an average age of 41.39±14.02 yr and a male to female ratio of 1:3.6.15 of 23 patients were diagnosed as idiopathic,3 related to Behcet's disease,3 related to systemic vasculitis,2 related to Mycobacterium tuberculosis infection.b)The Semi-quantitative score of TNF-? ranged from(++)(4.35%),(+)(60.87%)to(-)(34.78%)in 23 cases.The AOD of positive area was significantly higher in the study group compared with the normal control(p=0.047).c)The Semi-quantitative score of NF?B ranged from(++)(30.43%)to(+++)(69.57%)in 23 cases of EN.The AOD of positive area was significantly higher in the study group compared with the normal control(p=0.001).d)The Semi-quantitative score of STAT1 ranged from(+++)(28.57%),(++)(14.29%)to(+)(14.29%)in 14 cases.The AOD of positive area was significantly higher in the study group compared with normal control(p<0.001).e)The Semi-quantitative score of STAT3 ranged from(++)(66.67%)to(+)(33.33%)in 15 cases.The AOD of positive area was significantly higher in the study group compared with the normal control(p<0.001).f)The Semi-quantitative score of IFN-? ranged from(+)(17.39%)to(-)(82.61%)in 23 cases.As for AOD of positive area,there was no significant difference between the study group and the normal control(p=0.095).5.Conclusiona)This study further proved that there is significant increase of the expression of TNF-?,NF?B,STAT1 and STAT3 in the subcutaneous adipose tissue of EN lesions.It is speculated that there is abnormal activation of TNF-NF?B signaling pathway and JAK-STAT signaling pathway in this area,which may play an important role in the development of EN.b)There is no significant increase in IFN-y expression in subcutaneous adipose tissue of EN,which suggests IFN-y may not be related to the activation of TNF-NF?B signal pathway or JAK-STAT signal pathway in that area.