Low titre autoantibodies against recoverin in sera of patients with small cell lung cancer but without a loss of vision

Bazhin, Alexandr V.; Shifrina, Olga N.; Savchenko, M. A.; Тихомирова, Н. К.; Goncharskaia, Maria A.; Gorbunova, Vera; Senin, Ivan I.; Чучалин, А. Г.; Philippov, Pavel P.

doi:10.1016/s0169-5002(01)00212-4

Cited by 35 publications

(28 citation statements)

References 18 publications

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“…Western blot analysis detected reactivity against a few retinal protein bands in 33%, and against 5 or more retinal protein bands in 22%, ranging in weight from 13 to 148 kDa [30]. Autoantibodies have been found in numerous other retinal and systemic diseases, and in patients with cancer but no visual symptoms [50,51]. For example, various antiretinal antibodies have been identified in 10% of patients with retinitis pigmentosa [27], and in a case series of 30 patients with retinitis pigmentosa and cystoid macular oedema, antiretinal antibodies were found in 90% of cases [52].…”

Section: Antigens and Antibodiesmentioning

confidence: 99%

Autoimmune Retinopathy

Braithwaite

Vugler²,

Tufail

2012

Ophthalmologica

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Autoimmune retinopathy encompasses a spectrum of rare autoimmune diseases that primarily affect retinal photoreceptor function, and include cancer-associated retinopathy (CAR), melanoma-associated retinopathy (MAR) and presumed non-paraneoplastic autoimmune retinopathy (npAIR). Autoimmune retinopathy typically presents in the fifth and sixth decades with rapidly progressive, bilateral, painless visual deterioration but an unremarkable fundus examination. CAR, MAR and npAIR have an overlapping clinical phenotype, and extensive investigation is required to exclude other causes of retinopathy, and to identify any occult malignancy, before a presumptive diagnosis can be made. Delayed diagnosis, and treatment initiation relatively late in the disease course, may contribute to the poor visual prognosis. Various treatments have been attempted, including systemic immunosuppression with steroid and steroid-sparing agents, intravenous immunoglobulin, and plasmapheresis, but these lack an evidence base. A variety of antiretinal antibodies have been identified in patients with autoimmune retinopathy, including antibodies to recoverin, α-enolase and transducin-α, but seronegative disease is also common. Clinical access to specialised serological investigation is very limited internationally, and this exacerbates the management challenge presented by patients with suspected autoimmune retinopathy. Several decades of experimental research have resulted in very considerable advances in our understanding of the pathophysiological mechanisms that may underlie autoimmune retinopathy. However, the precise triggers which result in loss of ocular immune privilege and sudden autoimmune attack on retinal cells have yet to be elucidated. This review summarizes the classification, investigation and management of autoimmune retinopathy, and considers the evolving concepts about its immunological aetiology.

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Section: Antigens and Antibodiesmentioning

confidence: 99%

Autoimmune Retinopathy

Braithwaite

Vugler²,

Tufail

2012

Ophthalmologica

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“…The lung cancer is frequently accompanied by paraneoplastic neurological disorders with signs not related directly to the neoplastic tissue [2]. The past decade has brought a number of reports on the presence of autoantibodies to various retinal proteins in sera of patients with Jankowska/Witkowska/Porębska/ Kuropatwa/Kurowska/Gorczyca lung cancer [3][4][5][6][7]. Usually these antibodies were detected because of severe visual defects observed in patients by ophthalmologists even earlier to the cancer diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Serum Antibodies to Retinal Antigens in Lung Cancer and Sarcoidosis

et al. 2004

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Objective: Autoantibodies to various neuronal proteins frequently accompany lung cancer and their appearance may precede cancer symptoms. In this study we examined which retinal antigens (RAs) are recognized by sera of patients with lung cancer and whether the occurrence of serum antibodies to particular RAs is characteristic for cancer in comparison with a noncancer lung disease. Methods: Sera of 72 patients with non-small-cell lung cancer (NSCLC), 29 with small-cell lung cancer (SCLC), 27 with sarcoidosis (S), and sera of 32 healthy donors were examined in immunoblotting using retinal extracts and purified RAs as antigens. Results: 69.0% of SCLC, 45.8% of NSCLC, and 44.4% of S sera displayed anti-RAs reactivity. Significantly less (p < 0.05; χ² test) percent of healthy control sera reacted with RAs. Lung cancer sera recognized mainly 46-, 56-, and 36-kD and to a smaller extent also 96-, 72-, 43-, and 26-kD proteins. Most of them were recognized with about 2-fold lower frequencies by S and control sera. Only lung cancer sera contained very high-titer antibodies to 46- and 26-kD RAs, identified as α-enolase and recoverin, respectively. Conclusion: Antibodies to RAs occur more frequently and in higher titers in lung cancer (especially SCLC) than in sarcoidosis or control sera. Although antibodies to retinal α-enolase, recoverin and other RAs are present mainly or exclusively in lung cancer sera, none of them seems to be a specific marker of a particular disease.

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“…To generate AAR, tumor cells should express Rc mRNA and recoverin protein. The expression of AAR at the mRNA and/or protein levels has been shown for tumor tissues and/or cell lines in the case of lung tumors (7)(8)(9)(10), malignant melanoma (15,20) and breast, endometrial and cervical carcinomas (14). Recently, the recoverin-positive immune reaction was demonstrated for brain glioma and glioblastoma, squamous cell carcinoma, and carcinomas of the esophagus, stomach, colon, rectum, pancreas, kidney, prostate, ovary, neck of the uterus and breast; in addition, the ability of lung tumors to express recoverin was confirmed (21).…”

Section: Discussionmentioning

confidence: 99%

“…In certain patients with lung cancer, high-titer serum autoantibodies against recoverin (AAR) trigger the development of a PNS, cancer-associated retinopathy (CAR) (6,7). However, low-titer serum AAR of patients with lung cancer do not necessarily cause CAR syndrome (8)(9)(10). Instead, this syndrome only occurs in approximately 1% of cancer patients, whereas the frequencies of serum AAR in patients with small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) equal 15 and 20%, respectively (10).…”

Section: Introductionmentioning

confidence: 99%

Autoantibodies against the Ca2+-binding protein recoverin in blood sera of patients with various oncological diseases

Savchenko¹,

Goncharskaia²,

Skorikova³

et al. 2011

Oncology Letters

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Abstract. In cancer, the retinal Ca 2+ -binding protein recoverin is a paraneoplastic antigen, the aberrant expression of which is capable of triggering the appearance of specific autoantibodies in the serum of patients with malignant tumors and the subsequent development of a paraneoplastic syndrome, cancer-associated retinopathy (CAR). The frequency of serum autoantibodies against recoverin (AAR), earlier determined at a rate of 15-20% in lung cancer, is much higher than the frequency of CAR syndrome, which is approximately 1%. In the present study, we estimated for the first time the frequencies of serum AAR in patients with various types of malignancies other than lung cancer. Patient biospecimens were collected to analyze for the presence of AAR. Additionally, various cell lines were cultivated and analyses were performed using Western blotting and RT-PCR. Results showed that in all cases tested, the AAR frequencies did not exceed 10%. Five AAR-positive patients with various types of cancer were available for ophthalmological investigation and only one of these patients had CAR syndrome. This result is consistent with the conclusion made in our previous studies of lung cancer that serum AAR do not necessarily trigger the development of CAR syndrome. IntroductionNeuronal proteins, which are usually present only within the nervous system but may also be expressed in malignant tumors localized outside the nervous system, are assigned to paraneoplastic (onconeural) antigens (PNA). The immune system of certain patients responds to PNA by producing specific autoantibodies and/or cytotoxic T-cells that trigger the development of a paraneoplastic neurological syndrome (PNS) (1). One such PNA is the photoreceptor Ca 2+ -binding protein recoverin (2,3), which is normally specific to the retina and the pineal gland but may also be aberrantly expressed in malignant tumors of the lung and other tissues (4,5). In certain patients with lung cancer, high-titer serum autoantibodies against recoverin (AAR) trigger the development of a PNS, cancer-associated retinopathy (CAR) (6,7). However, low-titer serum AAR of patients with lung cancer do not necessarily cause CAR syndrome (8-10). Instead, this syndrome only occurs in approximately 1% of cancer patients, whereas the frequencies of serum AAR in patients with small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) equal 15 and 20%, respectively (10).By analogy with cancer-testis antigens, recoverin has been classified as a cancer-retina antigen (5) for the following reasons: i) its normal expression is restricted to an immunoprivileged tissue (retina), ii) it is aberrantly expressed in tumor cells, iii) it subsequently demonstrates high antigenicity (autoantibodies and/or T-cells), and iv) aberrant demethylation of the gene promoter is involved in the aberrant expression of recoverin (11).In this study, we analyzed serial specimens of blood sera of patients with a number of different malignancies to estimate the frequency of serum AAR in oncological disea...

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Low titre autoantibodies against recoverin in sera of patients with small cell lung cancer but without a loss of vision

Cited by 35 publications

References 18 publications

Autoimmune Retinopathy

Autoimmune Retinopathy

Serum Antibodies to Retinal Antigens in Lung Cancer and Sarcoidosis

Autoantibodies against the Ca2+-binding protein recoverin in blood sera of patients with various oncological diseases

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