Progranulin as marker for autoimmune disorders
Despite the availability of several diagnostic markers for autoimmune disorders there is still a need for further markers in order to expand and/orimprove diagnosis and treatment of autoimmune disorders. Progranulin is a secreted precursor protein with an N terminal signal peptide and seven granulin motifs. Diverse functions of progranulin and several receptors and interaction partners of progranulin have been identified so far. With regard to autoimmune diseases, the most interesting action of progranulin is its strong anti-inflammatory effect, which is mediated by its high affinity to TNF-α-receptors 1 and 2 with a strong inhibitory effect.
Scientist of the Medical Faculty of Saarland University found autoantibodies to progranulin in samples from subjects suffering from ANCA-associated and ANCA-negative primary systemic vasculitides as well as in other autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. In addition, they also identified progranulin with a specific posttranslational modification and aberrant forms of progranulin in these autoimmune patients. The inventors have furthermore demonstrated that anti-progranulin autoantibodies have a neutralizing effect on progranulin plasma levels, which is of particular interest in the light of progranulin’s function as a potent direct inhibitor of TNFR-1&2 and that the presence of anti-progranulin autoantibodies is significantly associated with active disease.
The invention offers a tool for the diagnosis of patients suffering from anautoimmune disorder, or patients with a suspected diagnosis of an autoimmune disease:
- detection of autoantibodies against progranulin
- detection of posttranslationally modified progranulin
- detection of aberrant fragments of progranulin
Each of these methods can be used alone or in combination. In addition, the identification of autoimmune patients with progranulin autoantibodies could possibly guide individualized therapeutic strategies because these patients should particularly profit from TNF blockers.
- Marker not restricted to a particular autoimmune disease, but specific for ongoing autoimmune process
- Detection in so far seronegative patients and autoimmune diseases possible
- Detection of progranulin autoantibodies could possibly guide individualized therapeutic strategies