Characterization of the autoantigen calreticulin

Area of Science:

• Immunology
• Molecular Biology
• Autoimmunity

Background:

• Anti-Ro/SS-A antibodies are prevalent in Sjögren's syndrome and SLE patients, and in mothers of infants with neonatal lupus.
• The cellular function of the Ro/SS-A ribonucleoprotein complex is currently unknown.
• Ro/SS-A autoantigens are implicated in autoimmune diseases and neonatal complications.

Purpose of the Study:

• To investigate the cellular function and immunoreactivity of Ro/SS-A autoantigens.
• To characterize the polypeptide encoded by the cDNA of a putative 60-kDa Ro/SS-A autoantigen.
• To determine if calreticulin is a Ro/SS-A autoantigen.

Main Methods:

• Oligonucleotide-directed cDNA isolation based on the amino-terminal sequence of a putative 60-kDa Ro/SS-A autoantigen.
• Sequence analysis and homology comparison of the isolated cDNA.
• Detection of autoantibodies in patient sera using immunoserological assays.

Main Results:

• The isolated cDNA encodes a polypeptide that is the human homologue of calreticulin, an endoplasmic reticulum calcium-binding protein.
• The encoded polypeptide shares significant identity with RAL-1, an antigen from Onchocerca volvulus.
• Contrary to previous reports, calreticulin was found not to be a Ro/SS-A autoantigen.
• Anticalreticulin autoantibodies were identified in sera from patients with Systemic Lupus Erythematosus (SLE) and onchocerciasis.

Conclusions:

• Calreticulin is not the Ro/SS-A autoantigen, despite sequence homology.
• The presence of anticalreticulin antibodies in SLE and onchocerciasis suggests a potential role in these conditions.
• Further research is needed to elucidate the precise role of calreticulin in autoimmune diseases and parasitic infections.