Clinical, biological and pharmacological keynotesAuto-antibodies in autoimmune hepatitis: Anti-soluble liver antigen (SLA)
Section snippets
Detection of anti-soluble liver antigen (SLA) antibodies
Anti-SLA antibodies cannot be revealed by indirect immunofluorescence on a common substrate but are detectable using radioimmunoassay, enzyme linked immunosorbent assays (Elisa), immunoblotting and dot blotting using native cytosolic antigen or recombinant 50 kDa protein identified as the UGA serine tRNA-protein complex [4], [5], [6] and, more recently, as o-phosphoseryl-tRNA: selenocysteinyl-tRNA synthase (SepSecS) [7]. In 2010, this identification of recombinant protein was confirmed by mass
Anti-soluble liver antigen (SLA) has been considered as a specific diagnostic marker of autoimmune hepatitis type 1 (AIH-1)
The frequency of anti-SLA in AIH-1 has been reported as being between 6% and 58% in adults and children [1], [4], [9], [10], [11], [12], [13], [14], [15], [16], [17], alone or in combination with ASMA and/or ANA. The lowest prevalence was found in patients from Japan [12], [13]. These antibodies have also been described in 15% to 30% of PBC/AIH overlap syndrome [4], [16]. However, their detection is particularly useful in patients without conventional antibodies, and they have enabled the
Prognostic value of anti-soluble liver antigen (SLA)
The prognostic value of antibodies to SLA has seldom been studied and remains controversial [14], [15], [16], [21]. Ma et al. [14] suggested that anti-SLA reactivity against conformational epitopes identified patients with a worse prognosis. However, their patients were children in whom the presentation and course of the disease were more severe than in adults.
An association between AIH recurrence after liver transplantation and antibodies to SLA has also been described (anti-SLA prevalence of
Anti-soluble liver antigen (SLA) and response to treatment
Previous studies in AIH-1 patients indicated that individuals with and without anti-SLA were similar in terms of their initial response to corticosteroid therapy [11], [15], [16], [21], [23]. It has been also shown that anti-SLA persist during the disease and its treatment [24]. However, seropositivity was associated with a higher frequency of relapse after corticosteroid withdrawal: the relapse rate among anti-SLA-positive patients in several studies was 14/14 (100%) compared with 74/102 (73%)
Anti-soluble liver antigen (SLA) in aetiopathogenesis of autoimmune hepatitis
Because anti-SLA have a high degree of specificity for AIH, are directed against a single antigen and are associated with relapse after corticosteroid withdrawal, they may reflect a pertinent pathogenic process more strongly than either ASMA or ANA [24]. Their association with DRB1*0301 may influence disease occurrence and severity by affecting auto-antigen presentation and/or by synergizing with other autoimmune promoters [24].
Concerning the structure of the antigen, SLA has sequence homology
Conclusion
In summary, antibodies to SLA are of major diagnostic value for AIH-1, including paediatric forms and overlap syndromes with cholestatic diseases. Their detection is particularly useful in patients who are negative for conventional markers of the disease (ANA, ASMA). The prognostic value of anti-SLA is controversial but they could be used to evaluate the risk of relapse of the inflammatory process after corticosteroid therapy and the recurrence of autoimmune hepatitis after orthotopic liver
Disclosure of interest
The authors declare that they have no conflicts of interest concerning this article.
References (25)
- et al.
Characterization of a new subgroup of autoimmune chronic active hepatitis by auto-antibodies against a soluble liver antigen
Lancet
(1987) - et al.
International autoimmune hepatitis group report: review of criteria for diagnosis of autoimmune hepatitis
J Hepatol
(1999) - et al.
Identification of target antigen for SLA/LP auto-antibodies in autoimmune hepatitis
Lancet
(2000) - et al.
Soluble liver antigen: isolation of a 35-kD recombinant protein (SLA-p-35) specifically recognizing sera from patients with autoimmune hepatitis
Hepatology
(2001) - et al.
SLA/Lp/tRNP(ser)sec antigen in autoimmune hepatitis: identification of the native protein in human hepatic cell extract
J Autoimmun
(2010) - et al.
Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexes in chronic hepatitis
Gastroenterology
(1993) - et al.
Clinical significance of auto-antibodies to soluble liver antigen in autoimmune hepatitis
J Hepatol
(1999) - et al.
Low frequency of anti-SLA/LP auto-antibodies in Japanese adult patients with autoimmune liver diseases: analysis with recombinant antigen assay
J Autoimmun
(2003) - et al.
Antibodies to conformational epitopes of soluble liver antigen define a severe form of autoimmune liver disease
Hepatology
(2002) - et al.
Antibodies to soluble liver antigen: an additional marker in type 1 autoimmune hepatitis
J Hepatol
(2000)
Antibodies to soluble liver antigen/liver pancreas and HLA risk factors for type 1 autoimmune hepatitis
Am J Gastroenterol
Simplified criteria for the diagnosis of autoimmune hepatitis
Hepatology
Cited by (7)
Presentation and outcomes of autoimmune hepatitis type 1 and type 2 in children: A single-center study
2021, Journal of Pediatric Gastroenterology and NutritionResearch advances in autoantibodies in autoimmune hepatitis
2020, Journal of Clinical HepatologyAutoantibody Profiling in a Cohort of Pediatric and Adult Patients With Autoimmune Hepatitis
2016, Journal of Clinical Laboratory AnalysisAutoantibody and human leukocyte antigen profiles in children with autoimmune liver disease and their first-degree relatives
2014, Journal of Pediatric Gastroenterology and NutritionJuvenile autoimmune hepatitis: Spectrum of the disease
2014, World Journal of Hepatology