Limited utility of plasma elafin as a biomarker for skin graft‐versus‐host disease following allogeneic stem cell transplantation

Abstract

Background. Acute cutaneous graft-versus-host disease (acGVHD) following haematopoietic stem cell transplant (HSCT) is common but difficult to distinguish from other causes of rash. Plasma elafin has been proposed as a diagnostic and prognostic biomarker of skin GVHD. Aim. To evaluate the role of plasma elafin as a biomarker in acGVHD in an Indian population. Methods. Plasma elafin was evaluated in a prospective study of HSCT recipients, conducted over 2 years, taking measurements at baseline and at onset of skin rash after HSCT. Patients were categorized into those with GVHD rash, those with non-GVHD rash and those with no rash and the three groups were compared. Results. Two hundred and sixty-one patients with a median age of 16 years (range 1-61 years) and a male predominance (175 : 86 M/F) underwent HSCT during the study period: 56 patients in the GVHD group, 49 in the non-GVHD group and 156 in the no-rash group. The median baseline elafin was similar in all three groups. At the onset of rash, median elafin level was similar between GVHD and non-GVHD rash (34 549 vs. 32 077 pg/mL; P = 0.58) and between GVHD and no rash (34 549 vs. 26 197 pg/mL; P = 0.08). A rise in elafin from baseline was significantly different between GVHD and no rash (P < 0.001) but not between GVHD and non-GVHD rash (P = 0.44). Conclusion. The utility of plasma elafin as a biomarker of skin GVHD is very limited. Plasma elafin, although elevated in cutaneous GVHD, is not helpful in distinguishing between GVHD rash and other causes of rash following HSCT.

Decreased Plasma Level of Cytokeratin 20 (KRT20) Is Indicative of the Emergence and Severity of Acute GvHD Irrespective to the Type of Organ Involvement

“…It has been demonstrated that elevated plasma level of PI3 correlates with cutaneous aGvHD and disease severity [19], and these initial findings have been confirmed by others as well [20]. Nevertheless, PI3 is inferior to REG3A as a prognostic marker when determining non-relapse mortality or over-all survival [21], and it has been suggested that PI3 may be inappropriate for the differential diagnosis of skin damage induced by cutaneous aGvHD [22]. Finally, the intestinal-type fatty acid-binding protein (FABP2) is another gut-restricted antimicrobial protein the dysregulation of which has been also reported in the blood in aGvHD [23,24].…”

Evaluation of elafin as a marker of skin fibrosis -a preliminary study

“…Moreover, Brüggen et al suggested an association between ela n expression in the skin and poor prognosis for patients with cutaneous GVHD (18). On the other hand, recent studies found no difference in ela n concentration between clinical stages of skin disease and no correlation with the 6month nonrelapse mortality as well as showed that ela n does not help to distinguish between GVHD skin lesions and other causes of rash following HSCT (7,11). In our study, patients suffering from GvHD presented the highest concentration levels of all analyzed groups of diseases, although, in contrast to previous reports, these were patients who quali ed as ccGvHD.…”

“…According to the subset classi cation of SSc, there were 35 patients with diffuse cutaneous (dcSSc) and 3 with limited cutaneous form (lSSc) based on the extent of their skin involvement. The patients' history included evaluation of skin involvement using modi ed Rodnan skin thickness score (11), lung and renal involvement.…”

Biomarkers for early complications post hematopoietic cell transplantation: Insights and challenges

“…Also, low tissue amphiregulin expression on immunohistochemistry has been reported in 74% of patients with acute gut GVHD and might aid in diagnosis without classic apoptotic changes ( 58 ). Similarly, tissue, and not plasma, elafin on immunohistochemistry can aid in diagnosing acute GVHD involving the skin ( 59 , 60 ).…”

“…Elafin was initially discovered to be associated with skin GVHD ( 48 ). However, its utility appears very limited owing to the lack of reproducibility ( 60 ). The inclusion of elafin to REG3α and ST2 was also shown to be of little value in improving the accuracy of assessing HSCT outcomes ( 109 ).…”