C-reactive protein is an ‘excellent biomarker’ for RDEB severity: Study
New insights about interplay between infection, immune response in RDEB
C-reactive protein (CRP), a standard marker for inflammation, is an indicator of the severity of recessive dystrophic epidermolysis bullosa (RDEB) but not of active skin infections, according to a recent study of inflammatory biomarkers.
“Our findings identify C-reactive protein as an excellent biomarker for disease severity in RDEB…. [and] provide new insights into the interplay of infection and immunological factors in the [development] of RDEB,” scientists wrote.
The study, “Unveiling the value of C-reactive protein as a severity biomarker and the IL4/IL13 pathway as a therapeutic target in recessive dystrophic epidermolysis bullosa: A multiparametric cross-sectional study,” was published in Experimental Dermatology.
RDEB is a severe form of epidermolysis bullosa caused by a lack of collagen type VII, a connective tissue protein that helps hold the layers of skin together. Without this protein, the skin becomes fragile and prone to tears and blisters.
Chronic skin wounds often cause inflammation, fibrosis
Chronic skin wounds often cause inflammation and fibrosis, or the buildup of scar tissue, which can progress to aggressive forms of skin cancer.
Anti-inflammatory medications can mitigate the negative effects of abnormal inflammatory responses in RDEB. However, suppressing the immune system can also lead to infection and sepsis, an extreme response to infection, which are the leading causes of hospitalization and death in RDEB patients.
“Understanding the immunological mechanisms is crucial for selecting medications that balance inflammation control and immunocompetence,” the researchers wrote. Immunocompetence is the ability to produce a normal immune response following exposure to an invader.
To identify inflammatory biomarkers and potential therapeutic targets, a team from Spain investigated the relationship between clinical severity and systemic (bodywide) inflammatory markers in a group of RDEB patients.
In total, 84 patients, ages 1-67, were recruited (40 of them were female). Among them, 13 participants (15%) had mild disease, 22 (27%) had moderate disease, and 49 (58%) were considered severe, according to the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI). A group of 71 healthy individuals served as controls. Various inflammation-related proteins were measured from blood samples.
Blood tests revealed elevated levels of CRP in 73% of RDEB patients, mainly those with severe (98%) or moderate disease (55%). CRP and EBDASI scores were significantly correlated, and a significantly higher risk of systemic inflammation — a CRP of more than 5 mg/L — could be predicted in patients with an EBDASI of over 95 points.
12 of 13 cytokines found elevated in patients
A total of 12 out of 13 immune signaling proteins, called cytokines, were elevated in RDEB compared with controls. Among those with mild disease, the cytokine TNF was increased, while 11 were elevated in moderate/severe cases, and the cytokine VEGFA rose in severe cases.
A correlation was revealed between elevated interleukin-13 (IL-13) and IL-4 cytokines with EBDASI scores and CRP levels. More than 60% of patients had high levels of IL-13, IL-4, and IL-6.
“These results underscore the IL4/IL13 pathways as potential evidence-based therapeutic targets,” the researchers suggested.
There was a high prevalence of antibodies, also known as immunoglobins (Ig), including IgA (78%), IgG (68%), IgE (41%), and IgM (15%). Notably, high levels of both IgA and IgG were found in 62% of patients, and their levels correlated with EBDASI scores and certain inflammatory factors.
IgE levels, an indicator of allergies, were markedly elevated in six patients (7.4%). Unexpectedly, seven RDEB patients (9%) had an antibody profile consistent with a primary immunodeficiency disease, a group of disorders in which part of the body’s immune system does not function normally.
No significant differences were found in CRP, the prevalence of IgA, IgG, or IgE abnormalities, or cytokine levels between severe RDEB patients with and without an active skin infection. This suggested the “inflammatory profile in patients with RDEB did not reflect the presence of [active skin infection] but rather a higher severity status,” the team wrote.
Results from patients with or without a history of skin infections, with similar EBDASI scores, revealed a link between a history of skin infections and CRP levels. There were also high levels of CRP among those who were hospitalized because of infection. A much higher percentage of these patients had IgM levels below the normal range than nonhospitalized patients (39% vs. 6%), indicating “a possible post-infection immunocompromise,” the researchers wrote.
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