Long-term survival of a patient with small cell lung cancer associated with cancer-associated retinopathy

Kobayashi, Makoto; Ikezoe, Takayuki; Uemura, Yoshiki; Ueno, Hideki; Taguchi, Hirokuni

doi:10.1016/j.lungcan.2007.02.015

Cited by 22 publications

(10 citation statements)

References 33 publications

(21 reference statements)

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“…Patients with CAR and MAR have a high mortality rate on account of the underlying malignancy. Interestingly, several studies suggest that patients with CAR who are seropositive for antirecoverin antibody may have improved survival compared to those who are seronegative [79,83]. It has been hypothesized that this results from peripheral activation of recoverin-specific antitumour cytotoxic T-lymphocytes [79].…”

Section: Prognosismentioning

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: Prognosismentioning

confidence: 99%

Autoimmune Retinopathy

Braithwaite

Vugler²,

Tufail

2012

Ophthalmologica

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“…In addition, low levels of anti-recoverin autoantibodies have been also reported in individuals with lung and other cancers without visual symptoms but not in normal subjects [23], indicating their connection to initial anti-tumor responses. Interestingly, SCCL patients with anti-recoverin antibodies have better survival without SCCL recurrence than SCCL patients who lack anti-recoverin antibodies [24], suggesting that these antibodies pay a double role, a positive as a part of the anti-tumor immune response, and a negative in the induction of retinal degeneration.…”

Section: Association Of Car and Mar With Anti-retinal Autoantibodiesmentioning

confidence: 99%

Autoantibody targets and their cancer relationship in the pathogenicity of paraneoplastic retinopathy

Adamus

2009

Autoimmunity Reviews

186

160

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Paraneoplastic retinopathies (PR), including cancer-associated retinopathy (CAR) or the closely related melanoma-associated retinopathy (MAR) occur in a small subset of patients with retinal degeneration and systemic cancer. This autoimmune syndrome is characterized by sudden, progressive loss of vision in association with circulating anti-retinal autoantibodies. The PR syndromes are heterogeneous, may produce a number of ocular symptoms, and may be associated with several different neoplasms, including lung, breast, prostate, gynecological, and colon cancer, melanoma, and hematologic malignancies. We examined the onset of retinopathy in correlation to the diagnosis of cancer and the presence of specific anti-retinal autoantibodies in PR patients. In some patients without diagnosed malignant tumors, the onset of ocular symptoms and the presence of autoantibodies preceded the diagnosis of cancer by months to years, including anti-recoverin, antitransducin-α, and anti-carbonic anhydrase II antibodies. Although anti-retinal autoantibodies may not be a good predictor of a specific neoplasm, they can be used as biomarkers for different subtypes of retinopathy. Identification of autoantibodies involved in autoimmune-mediated PR will help elucidate the mechanisms underlying the PR syndromes and develop targeted therapies for these sight-threatening disorders. KeywordsCancer-associated retinopathy; anti-retinal autoantibodies; recoverin; enolase; autoimmune retinopathy Take home message• Retinal autoantigens can be used as biomarkers for different subtypes of CAR.• Autoantibodies to retinal antigens that also recognize tumor autoantigens may be useful biomarkers for the cause and origin of paraneoplastic disease.• In some patients, the onset of ocular symptoms and the detection of anti-retinal autoantibodies may precede the diagnosis of systemic cancer.• The recognition of retinopathy as part of a paraneoplastic syndrome should prompt an immediate search for an occult neoplasm.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. • Early detection of anti-retinal autoantibodies may serve to identify those who are at risk of retinal deterioration and blindness. NIH Public Access

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“…The existence of multiple SCLC-associated autoimmune syndromes suggests an interplay between SCLC and the immune system. SCLC patients with autoimmune syndromes exhibit high titer antibodies against neuronal proteins ectopically expressed by their tumors and can show regression (Dalmau et al, 1992; Winter et al, 1993; Darnell and DeAngelis, 1993; Graus et al, 1997; Honnorat et al, 2009; Kobayashi et al, 2007; Kazarian and Laird-Offringa, 2011). Although the high titer patients are rare, the characteristic autoantibodies are found in a substantial fraction of SCLC patients without autoimmune symptoms, albeit at lower titers (Graus et al, 1997; Kazarian and Laird-Offringa, 2011; Dalmau et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Isoaspartylation appears to trigger small cell lung cancer-associated autoimmunity against neuronal protein ELAVL4

Pulido¹,

DerHartunian²,

Qin³

et al. 2016

Journal of Neuroimmunology

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Autoantibodies against SCLC-associated neuronal antigen ELAVL4 (HuD) have been linked to smaller tumors and improved survival, but the antigenic epitope and mechanism of autoimmunity have never been solved. We report that recombinant human ELAVL4 protein incubated under physiological conditions acquires isoaspartylation, a type of immunogenic protein damage. Specifically, the N-terminal region of ELAVL4, previously implicated in SCLC-associated autoimmunity, undergoes isoaspartylation in vitro, is recognized by sera from anti-ELAVL4 positive SCLC patients and is highly immunogenic in subcutaneously injected mice and in vitro stimulated human lymphocytes. Our data suggest that isoaspartylated ELAVL4 is the trigger for the SCLC-associated anti-ELAVL4 autoimmune response.

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Long-term survival of a patient with small cell lung cancer associated with cancer-associated retinopathy

Cited by 22 publications

References 33 publications

Autoimmune Retinopathy

Autoimmune Retinopathy

Autoantibody targets and their cancer relationship in the pathogenicity of paraneoplastic retinopathy

Isoaspartylation appears to trigger small cell lung cancer-associated autoimmunity against neuronal protein ELAVL4

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