抗SLA/LP抗體的靶抗原參與selenprotein(一種UGA抑制物，tRNA相關蛋白)生物合成的調節，早期的研究也表明抗 SLA抗體有可能參與了對肝細胞的破壞，因此推測抗SLA/LP抗體與自身免疫性肝炎（AIH）的發病機制有關。雖然AIH存在種類較多的自身抗體，但多數自身抗體并非AIH特異性抗體?？?span>SLA/LP抗體為少數公認的AIH高度特異性自身抗體，在AIH所有相關自身抗體中最具有診斷價值?？?span> SLA/LP抗體在 AIH中的陽性率為10%～30%，該抗體多出現在ANA, SMA和抗LKM-1抗體陰性的AIH患者血清中?？?span>SLA/LP抗體為AIH-Ⅲ型的血清學標志，臨床上常用于AIH的診斷和鑒別診斷。陽性患者多為年輕女性，多伴有高免疫球蛋白血癥。約30%的AIH-Ⅲ型僅該抗體陽性，而缺乏所有其他自身抗體標志，但對免疫抑制治療有效，抗SLA抗體測定對發現這一部分AIH患者有重要意義。
New additions to DIARECT’s liver panel: SLA/LP antigen and human chimeric SLA/LP antibody
Autoimmune hepatitis (AIH) is a chronic, progressive inflammation of the liver and was first described in 1965 by Mackay et al. It was hypothesized that pathogenesis comprises environmental triggers, failure of immune tolerance mechanism and genetic predisposition (Vergani et al. 2002).
The disease does not exhibit pathognomonic symptoms; therefore diagnosis should combine clinical, serological, histological and genetic parameters. When diagnosed correctly, AIH is usually responsive to immuno-suppressive therapy. In the end stage the only therapeutic approach remaining is a liver transplantation (Costa et al. 2000).
Two types of AIH have been classified: AIH-2 and AIH-1. AIH-1 is most common and characterized by antinuclear antibodies (ANA) and smooth muscle antibodies (SMA). Detection of SLA/LP autoantibodies indicate a more severe progression of both types of the disease. AIH-2 is typified by seropositivity of patients with LKM1 and LC1 autoantibodies (Costa et al. 2000; Gelpi et al. 1992).
SLA/LP was first reported in supernatant of liver and kidney homogenates by Manns et al. 1987. It is a cytosolic soluble liver antigen / liver pancreas antigen specifically detected in about 20% of the patients with AIH. The target of anti-SLA/LP is a approx. 50-kDa UGA serine tRNA-associated protein complex (tRNP(Ser) Sec) (Wies et al. 2000). Costa et al. 2000 showed a high specificity and frequency (47, 5 %) of anti-tRNP (Ser) Sec autoantibodies for severe forms of type-1 AIH.
The RNA is a UGA suppressor serine tRNA (tRNA (Ser) Sec) and it functions in the pathway of selenoprotein synthesis in human cells. The tRNA is a requisite for co-translational incorporation of selenocystein into growing polypeptide chains. Therefore the RNA is shared with serine to seryl-tRNA and then converted to selenocysteyl-tRNA sec by the action of a selenocysteine synthase (Bock et al. 1991).
Diagnostic assays for autoantibody detection requires reference material to determine cut-off values and assay integrity. Mostly, pools of disease state serum or plasma are used. Main drawbacks of these standards are limited availability and variability. More consistent is the advanced use of chimeric monoclonal antibodies as positive controls in IVD kit development. This approach ensures consistent concentration, specificity and avidity, and furthermore eliminates safety and ethical concerns.