Anti–α-Fodrin Antibodies in Sjögren Syndrome and Lupus Erythematosus

Watanabe, Takahiro; Tsuchida, Takaaki; Kanda, Naoko; Mori, Katsunori; Hayashi, Yoshio; Tamaki, Kunihiko

doi:10.1001/archderm.135.5.535

Cited by 50 publications

(26 citation statements)

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“…We have established and investigated an animal model of SS in NFS/sld-mutant mice thymectomized 3 days after birth and found that the 120-kd ␣-fodrin protein is a critical autoantigen in the development of SS in this mouse model (12)(13)(14). Furthermore, we and other investigators (12,15) have found that patients with SS have high titers of serum anti-␣-fodrin antibody, suggesting that ␣-fodrin is a critical autoantigen for the onset or progression of human SS. Although the mechanism of autoimmune disorders in the lacrimal and salivary glands in this mouse model is still unclear, autoreactive CD4ϩ T cells are responsible for the destruction of the lacrimal and salivary glands in this model (16)(17)(18) as well as in human SS (19,20).…”

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confidence: 80%

Effective treatment of a mouse model of Sjögren's syndrome with eyedrop administration of anti‐CD4 monoclonal antibody

Hayashi¹,

Ishimaru²,

Arakaki³

et al. 2004

Arthritis & Rheumatism

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Objective. To determine whether eyedrop administration of an anti-CD4 monoclonal antibody (mAb) is effective in the treatment of Sjögren's syndrome (SS) using a mouse model of the disease.Methods. The anti-CD4 mAb was administered daily into the eyes of mice with SS from ages 4 to 8 weeks or ages 10 to 12 weeks. During treatment, tear volume was monitored and after final treatment, histologic features of the lacrimal and salivary glands, the phenotypes and function of T cells, and serum titers of anti-␣-fodrin antibody were examined.Results. Eyedrop administration of anti-CD4 mAb before the onset of SS prevented the autoimmune pathology seen in the lacrimal glands but not that in the salivary glands. Furthermore, eyedrop administration of anti-CD4 mAb after the development of SS inhibited mononuclear cell infiltration and the destruction of parenchyma only in the lacrimal glands. Eyedrop administration of anti-CD4 mAb suppressed the local activation of CD4؉ T cells rather than deleting CD4؉ T cells, which reduced the expansion of pathologic CD4؉ T cells against ␣-fodrin.Conclusion. These results demonstrate the remarkable efficacy of anti-CD4 mAb eyedrops in the treatment of SS eye symptoms, which illustrates a new antibody-based therapeutic strategy for patients with eye problems caused by SS as well as other diseases.

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confidence: 80%

Effective treatment of a mouse model of Sjögren's syndrome with eyedrop administration of anti‐CD4 monoclonal antibody

Hayashi¹,

Ishimaru²,

Arakaki³

et al. 2004

Arthritis & Rheumatism

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“…Regarding the immune system, focus has been on the B cells, due to the high prevalence of autoantibodies [1][2][3]. Although B cell hyperactivity has indeed been described [4,5], the question remains whether these alterations are B cell-intrinsic or caused by alterations in other parts of the immune system, such as innate immunity.…”

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confidence: 99%

Systemic increase in type I interferon activity in Sjögren's syndrome: A putative role for plasmacytoid dendritic cells

et al. 2008

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In the salivary glands of primary Sjögren's syndrome (pSjS) patients, type I IFN activity is increased, but systemic levels of type I IFN proteins are rarely detected. This study focused on the systemic activity of type I IFN in pSjS, as well as the role of peripheral plasmacytoid dendritic cells (pDC). Monocytes obtained from pSjS patients showed an increased expression of 40 genes. Twenty-three of these genes (58%), including IFI27, IFITM1, IFIT3 and IFI44, were inducible by type I IFN. pSjS serum had an enhanced capability of inducing IFI27, IFITM1, IFIT3 and IFI44 in the monocytic cell line THP-1, likely due to the action of IFN-b. This effect could be inhibited by blocking the type I IFN receptor, supporting a high type I IFN bioactivity in pSjS serum. In addition, circulatory pDC showed increased expression of CD40. This expression was correlated to the expression level of the type I IFN-regulated genes IFI27 and IFITM1 in monocytes of the same individual. This study indicates that the increased type I IFN activity observed in pSjS patients is not only a local but also a systemic phenomenon and points to pDC as a possible source of this activity.

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“…These cryptic epitopes may subsequently induce an autoimmune response. Interestingly, induction of apoptosis in a T-cell hybridoma results in the formation of 120-kDa ␣-fodrin (Martin et al, 1995;Vanags et al, 1996), to which autoantibodies have been detected in serum of patients with Sjögren's syndrome (Haneji et al, 1997;Watanabe et al, 1999). This illustrates that apoptosis may indeed play a role in the pathogenesis of Sjögren's syndrome.…”

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confidence: 97%

Apoptosis and Apoptosis-Related Molecules in the Submandibular Gland of the Nonobese Diabetic Mouse Model for Sjögren's Syndrome: Limited Role for Apoptosis in the Development of Sialoadenitis

Blokland

Helden-Meeuwsen

Wierenga‐Wolf

et al. 2003

Laboratory Investigation

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SUMMARY:Sjögren's syndrome is an autoimmune disease in which lymphocytic infiltrates develop in the exocrine glands.Pathogenetic aspects of the disease can be studied in the nonobese diabetic (NOD) mouse strain, a spontaneous model for Sjögren's syndrome. Apoptosis may play a role in the initation phase and in the effector phase of autoimmune diseases. Here, we have examined the role of apoptosis in the development of sialoadenitis in the NOD mouse. Apoptotic cells and the expression of apoptosis-related molecules were studied in submandibular glands (SMG) of NOD and NOD-scid mice before and after the onset of sialoadenitis. Numbers of apoptotic cells were not increased as compared with control mice, at any age. By immunohistochemistry, we demonstrated increased expression of Fas, Fas ligand (FasL), and bcl-2 on SMG epithelial cells of NOD and NOD-scid mice, as early as 3 days of age. mRNA expression of Fas and FasL was also examined in SMG by RQ-PCR. Low-level expression of Fas and FasL mRNA was observed in all mouse strains, from 1 day of age onward. We conclude that increased protein expression of Fas and FasL on SMG epithelial cells of NOD and NOD-scid mice probably indicates a genetically programmed abnormality in these cells that may form a trigger for the development of sialoadenitis in NOD mice. Because increased numbers of apoptotic cells were not observed, a role for actual apoptosis in the initiation or effector phase of sialoadenitis in the NOD mouse is unlikely. (Lab Invest 2003, 83:3-11).

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Anti–α-Fodrin Antibodies in Sjögren Syndrome and Lupus Erythematosus

Cited by 50 publications

References 35 publications

Effective treatment of a mouse model of Sjögren's syndrome with eyedrop administration of anti‐CD4 monoclonal antibody

Effective treatment of a mouse model of Sjögren's syndrome with eyedrop administration of anti‐CD4 monoclonal antibody

Systemic increase in type I interferon activity in Sjögren's syndrome: A putative role for plasmacytoid dendritic cells

Apoptosis and Apoptosis-Related Molecules in the Submandibular Gland of the Nonobese Diabetic Mouse Model for Sjögren's Syndrome: Limited Role for Apoptosis in the Development of Sialoadenitis

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