Complex HLA association in paraneoplastic cerebellar ataxia with anti-Yo antibodies

Hillary, Ryan; Ollila, Hanna; Lin, Ling; Desestret, Virginie; Rogemond, Véronique; Picard, Géraldine; Small, Mathilde; Arnulf, Isabelle; Dauvilliers, Yves; Honnorat, Jérôme; Mignot, Emmanuel

doi:10.1016/j.jneuroim.2017.12.012

Cited by 17 publications

(18 citation statements)

References 53 publications

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“…10 There is a differential genetic susceptibility to anti-Yo per cancer with primary human lymphocyte antigens class II involvement. 11 The combination of ACTH, intravenous immunoglobulin, and rituximab, with or without transitioning to dexamethasone for maintenance prior to weaning, has been successful in children with opsoclonus-myoclonus syndrome, both clinically and against neuroinflammation. 6 Rituximab (anti-CD20) targets B cells.…”

Section: Discussionmentioning

confidence: 99%

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Intensive Combination Immunotherapy and Neuroinflammation Resolution in a Child With Anti-PCA-1 (Yo) Paraneoplastic Syndrome and 2 Malignancies

Philipps

Tate

Pranzatelli

2018

Child Neurology Open

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Paraneoplastic cerebellar degeneration is rare and noteworthy in children. In this 7-year-old, it was documented to have occurred within a year of ataxia presentation. The instigating cancer was stage III adrenal adenocarcinoma, remitted after surgical resection at age 2. When her severe ataxia progressed, neuroinflammation was characterized by high cerebrospinal fluid Purkinje cell cytoplasmic antibody type 1 titers, oligoclonal bands, and neurofilament light chain. The immunotherapy strategy was to replace IV methylprednisolone, which lowered Purkinje cell cytoplasmic antibody type 1 titers without clinical improvement, with induction of adrenocorticotropic hormone/intravenous immunoglobulin/rituximab (ACTH/IVIG/rituximab) combination immunotherapy, ACTH/dexamethasone transition, and intravenous immunoglobulin maintenance. She became self-ambulatory and cerebrospinal fluid inflammatory markers regressed. Down syndrome predisposed her to a second cancer, pre-B acute lymphoblastic leukemia, 4 years later. Despite reversible cytosine arabinoside-provoked cerebellar toxicity, the ataxia is stable on monthly intravenous immunoglobulin without relapse, now 5 years after initial diagnosis. This report illustrates the use of cerebrospinal fluid biomarkers to detect, target, and monitor neuroinflammation, and successful combinations of immunotherapy to better the quality of life.

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Section: Discussionmentioning

confidence: 99%

“…10 There is a differential genetic susceptibility to anti-Yo per cancer with primary human lymphocyte antigens class II involvement. 11…”

Section: Discussionmentioning

confidence: 99%

Intensive Combination Immunotherapy and Neuroinflammation Resolution in a Child With Anti-PCA-1 (Yo) Paraneoplastic Syndrome and 2 Malignancies

Philipps

Tate

Pranzatelli

2018

Child Neurology Open

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“…The infrequency of anti-Yo antibody-associated PCD among patients with gynecological cancers could also reflect predisposing factors such as a genetic susceptibility. Hillary and colleagues conducted high resolution HLA class I and class II genotyping in 40 patients with PCD vs. ethnically matched controls (11). They provided evidence for association of the DRB1 * 13:01∼DQA1 * 01:03∼DQB1 * 06:03 haplotype with ovarian cancer-associated, but not breast cancer-associated, PCD (present in 9 of 29 cases).…”

Section: Genetic Basis Of Pcdmentioning

confidence: 99%

“…Paraneoplastic cerebellar degeneration (PCD), one of the most common paraneoplastic neurological syndromes (11), represents a heterogeneous group that differs in clinical features, prognosis, associated tumor and associated antibody (7) ( Table 1).…”

Section: Introductionmentioning

confidence: 99%

Immunological Bases of Paraneoplastic Cerebellar Degeneration and Therapeutic Implications

2020

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Paraneoplastic cerebellar degeneration (PCD) is a rare immune-mediated disease that develops mostly in the setting of neoplasia and offers a unique prospect to explore the interplay between tumor immunity and autoimmunity. In PCD, the deleterious adaptive immune response targets self-antigens aberrantly expressed by tumor cells, mostly gynecological cancers, and physiologically expressed by the Purkinje neurons of the cerebellum. Highly specific anti-neuronal antibodies in the serum and cerebrospinal fluid represent key diagnostic biomarkers of PCD. Some anti-neuronal antibodies such as anti-Yo autoantibodies (recognizing the CDR2/CDR2L proteins) are only associated with PCD. Other anti-neuronal antibodies, such as anti-Hu, anti-Ri, and anti-Ma2, are detected in patients with PCD or other types of paraneoplastic neurological manifestations. Importantly, these autoantibodies cannot transfer disease and evidence for a pathogenic role of autoreactive T cells is accumulating. However, the precise mechanisms responsible for disruption of self-tolerance to neuronal self-antigens in the cancer setting and the pathways involved in pathogenesis within the cerebellum remain to be fully deciphered. Although the occurrence of PCD is rare, the risk for such severe complication may increase with wider use of cancer immunotherapy, notably immune checkpoint blockade. Here, we review recent literature pertaining to the pathophysiology of PCD and propose an immune scheme underlying this disabling disease. Additionally, based on observations from patients' samples and on the pre-clinical model we recently developed, we discuss potential therapeutic strategies that could blunt this cerebellum-specific autoimmune disease.

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“…8 However, very recently, a potential HLA genetic predisposition to anti-Yo PCD in the context of a specific cancer has been pinpointed. 9…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic immune profiling of ovarian cancers in paraneoplastic cerebellar degeneration associated with anti-Yo antibodies

et al. 2018

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Complex HLA association in paraneoplastic cerebellar ataxia with anti-Yo antibodies

Cited by 17 publications

References 53 publications

Intensive Combination Immunotherapy and Neuroinflammation Resolution in a Child With Anti-PCA-1 (Yo) Paraneoplastic Syndrome and 2 Malignancies

Intensive Combination Immunotherapy and Neuroinflammation Resolution in a Child With Anti-PCA-1 (Yo) Paraneoplastic Syndrome and 2 Malignancies

Immunological Bases of Paraneoplastic Cerebellar Degeneration and Therapeutic Implications

Transcriptomic immune profiling of ovarian cancers in paraneoplastic cerebellar degeneration associated with anti-Yo antibodies

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