scholarly journals Exploration of Anti-Yo and Anti-Hu paraneoplastic neurological disorders by PhIP-Seq reveals a highly restricted pattern of antibody epitopes

2018 ◽  
Author(s):  
Brian D O'Donovan ◽  
Caleigh Mandel-Brehm ◽  
Sara E Vazquez ◽  
Jamin Liu ◽  
Audrey V Parent ◽  
...  

Paraneoplastic neurological disorders (PNDs) are immune-mediated diseases of the nervous system understood to manifest as part of a misdirected anti-tumor immune response. Identifying PND-associated autoantibodies and their cognate antigens can assist with proper diagnosis and treatment while also enhancing our understanding of tumor-associated immune processes, triggers for autoimmune disease, and the functional significance of onconeuronal proteins. Here, we employed an enhanced version of phage display immunoprecipitation and sequencing (PhIP-Seq) leveraging a library of over 731,000 unique phage clones tiling across the entire human proteome to detect autoantibodies and create high-resolution epitope profiles in serum and CSF samples from patients suffering from two common PNDs, the anti-Yo (n = 36 patients) and anti-Hu syndromes (n = 44 patients). All patient samples positive for anti-Yo antibody by a validated clinical assay yielded polyspecific enrichment of phage presenting peptides from the canonical anti-Yo (CDR2 and CDR2L) antigens, while 38% of anti-Hu patients (17/44) had a serum and/or CSF sample that significantly enriched peptides deriving from the ELAVL family of proteins, the anti-Hu autoantigenic target. The anti-Hu antibodies showed a remarkably convergent antigenic signature across 15/17 patients corresponding to residues surrounding and including the degenerate motif, RLDxLL, shared by ELAVL2, 3 and 4. Lastly, PhIP-Seq identified several known and novel autoantigens in these same patient samples, representing potential biomarkers that could aid in the diagnosis and prognosis of PND and cancer.

Author(s):  
John C. Probasco

Paraneoplastic neurological disorders (PNDs) are estimated to affect approximately 0.01% of all patients with cancer. The majority of PNDs are thought to be the byproduct of immune-mediated processes directed against tumor-related antigens, processes which are sometimes effective against a systemic cancer. The inciting cancer is often asymptomatic or occult, with patients presenting to the neurologist with a variety of neurological symptoms and signs depending on the area(s) of the central, peripheral, and autonomic nervous system involved. The diagnosis of a PND is reserved for patients with histologically proven cancer; however, clinical presentation and diagnostic test results may make the diagnosis of a PND highly probable in the absence of the diagnosis of a cancer.


1999 ◽  
Vol 46 (5) ◽  
pp. 774-777 ◽  
Author(s):  
Albert Saiz ◽  
Francesc Graus ◽  
Josep Dalmau ◽  
Alex Pifarr� ◽  
Concepci� Mar�n ◽  
...  

2004 ◽  
Vol 6 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Steven Vernino ◽  
Brian Patrick O'Neill ◽  
Randolph S. Marks ◽  
Judith R. O'Fallon ◽  
David W. Kimmel

2021 ◽  
Vol 14 ◽  
pp. 175628642098532
Author(s):  
Michelle F. Devine ◽  
Naga Kothapalli ◽  
Mahmoud Elkhooly ◽  
Divyanshu Dubey

We provide an overview of the varied presentations of paraneoplastic neurological syndromes. We also review the onconeural antibodies and their particular oncological and neurological associations. Recognition of these syndromes and their oncological associations is crucial, as early diagnosis and management has been associated with better patient outcomes. Specific management strategies and prognosis vary widely depending on the underlying etiology. An understanding of the relevant clinical details, imaging findings, and other diagnostic information can help tailor treatment approaches. We provide an outline of the diagnostic evaluation and treatment of various paraneoplastic neurological disorders, presenting with central and/or peripheral nervous system involvement. We briefly discuss neurologic immune checkpoint inhibitor-related adverse events, which can occasionally present with paraneoplastic neurological syndrome phenotypes.


2020 ◽  
Vol 21 (12) ◽  
pp. 4351
Author(s):  
Yuko Abe ◽  
Kiyoharu Fukushima ◽  
Yuki Hosono ◽  
Yuki Matsumoto ◽  
Daisuke Motooka ◽  
...  

The incidence and prevalence of non-tuberculous mycobacteria (NTM) infections are steadily increasing worldwide, partially due to the increased incidence of immunocompromised conditions, such as the post-transplantation state. The importance of proper diagnosis and management of NTM infection has been recently recognized. Host immunological responses play integral roles in vulnerability to NTM infections, and may contribute to the onset of specific types of NTM infection. Furthermore, distinct NTM species are known to affect and attenuate these host immune responses in unique manners. Therefore, host immune responses must be understood with respect to each causative NTM species. Here, we review innate, cellular-mediated, and humoral immunity to NTM and provide perspectives on novel diagnostic approaches regarding each NTM species.


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