This post-translational modification leads to more SLE specific SmD1 and SmD3 epitopes (B). enzyme immunoassayIFNARinterferon-/ receptorIIFTindirect immunofluorescence testLAIR1Leukocyte-associated immunoglobulin-like receptor 1LIAline immunoassayLIR1leukocyte immunoglobulin-like receptor-1MCTDmixed connective tissue diseasePAMPspathogen-associated molecular patternsPD-1(L)programmed Cell Death (Ligand) 1RIAradioactive immunoassayRNPribonucleoproteinSLESystemic lupus erythematosusSLICCSystemic Lupus International Collaborating ClinicsSnRNASmall nuclear RNAsnRNPsmall nuclear ribonucleoproteinTLRToll-like receptor 1.?Introduction Systemic lupus erythematosus (SLE) is a chronic, systemic rheumatic autoimmune disease, which is characterized by autoantibodies and immune complex deposition, which can basically affect any organ leading to a range of clinical manifestations. Besides clinical manifestations, serological findings play an important role in diagnosis. Because diagnostic criteria are lacking, classification criteria, which are primarily designed for including patients for clinical studies, are often used for diagnostic purposes. In 1971, the first classification criteria for SLE were described, which were first revised in 1982. These revised criteria included, amongst fluorescence antinuclear antibody (ANA) and antibody to native DNA, antibody against the Smith (Sm) antigen, which improved the performance of the criteria [1]. These antibodies, including antiphospholipid autoantibodies, which have been incorporated in the criteria since 1982, are nowadays still part of the SLE classification criteria, The European Alliance of Associations for Rheumatology (EULAR; formerly known as European League Against Rheumatism)/American College of Rheumatology (ACR) classification criteria, as well as the Systemic Lupus International Collaborating Clinics (SLICC) criteria. Besides the presence of autoantibodies, the SLICC criteria comprises additional serological criteria, such as low complement levels (C3, C4 or CH50) and a positive direct Coombs test in the absence of haemolytic anaemia [[2], [3], [4]]. In the 2019 EULAR/ACR criteria, ANA, tested by immunofluorescence on HEp-2?cells or an equivalent solid-phase ANA screening immunoassay, was introduced as an entry criterion Ko-143 hereby excluding ANA negative patients to be classified as having SLE [2,5]. In addition, in the 2019 EULAR/ACR criteria, within both clinical and immunology domains different criteria have been appointed different weights. Antibodies against the Smith (Sm) antigen have been assigned 6 points within the immunology domain, which is more than half of the total score required for SLE classification [2]. 2.?The Smith antigen The name Smith antigen is derived from a patient named Stephanie Smith, who was diagnosed with SLE in 1959. Her physician dr. Tan, discovered a specific SLE antigen using the Ouchterlony agar diffusion method with her serum. This specific SLE antigen became known as the Smith antigen or Sm antigen [6,7]. Ko-143 The Sm antigen represents not a single protein but a protein complex consisting of a group of core proteins. So far several proteins, being SmB1 (SmB), SmB2 (SmB), SmB3 (SmN), SmD1, SmD2, SmD3, SmE, SmF and SmG, have been identified, which are expressed in the nuclei of all cells [8]. The Sm proteins, together with ribonucleoproteins and small nuclear Ko-143 RNA (snRNA) form a RNA-protein complex or small nuclear ribonucleoprotein (snRNP), which is involved in precursor messenger RNA (mRNA) splicing, a process which ultimately leads to mature mRNA generation [9]. The Sm protein complex binds to the snRNA as a ring-liked structure, hereby protecting the snRNA from degradation by nucleases and supporting RNA-processing. There are different snRNAs known that are part of different snRNPs (e.g. U1, U2, U4/U6 and U5). U1-SnRNP is an example of a well-known spliceosome, which consists of U1-RNA, the ribonucleoproteins RNP70, A and C and Sm Proteins (Fig. 1). U1-snRNP also plays a role in RNA Ko-143 processing (e.g. polyadenylation). Interestingly, antibodies against U1-RNP are present in all patients with mixed connective tissue disease (MCTD), a condition that shares clinical features with SLE [10]. Open in a separate window Fig. 1 The U1 Rabbit Polyclonal to MDM4 (phospho-Ser367) small nuclear ribonucleoprotein complex. The U1 small nuclear ribonucleoprotein (U1-snRNP) complex consists of the Sm protein complex, which includes 9 different proteins (B1, B2 and B3, D1, D2, D3, E, F and G), ribonucleoproteins (RNP 70?KDa, RNP A and RNP C) and U1 ribonucleic acid (U1 RNA). RNA: ribonucleic acid; RNP: ribonucleoproteins; Sm: Smith protein. The Sm proteins are highly conserved in eukaryotes and share highly conserved motifs (Sm motif 1 en motif 2), which are involved in the interactions between the different Sm proteins [8,11,12]. 3.?The formation of anti-Sm antibodies in SLE patients Many autoantibodies have been described in SLE, but only a few antibodies, including anti-dsDNA, anti-Ro/La and anti-Sm, can be detected more frequent in SLE patients [[13], [14], [15]]. Ko-143 Anti-Sm antibodies, which were first identified in 1966, are detected in approximately 5C30%, depending on ethnicity and detection method used to identify the antibodies. Anti-Sm antibodies.
This post-translational modification leads to more SLE specific SmD1 and SmD3 epitopes (B)