Case Discussion Michael Wilson, MD, MAS UCSF MS and - - PowerPoint PPT Presentation

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Case Discussion Michael Wilson, MD, MAS UCSF MS and - - PowerPoint PPT Presentation

Jun 22, 2023 244 likes •286 views

2/9/2017 Uveitis 38 per 100,000 persons in the U.S. Mean age of onset is 30 years old 50% of cases are idiopathic Case Discussion Michael Wilson, MD, MAS UCSF MS and Neuroinflammation Center Uveitis and Neurologic Disease Case

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2/9/2017 1

Case Discussion

Michael Wilson, MD, MAS UCSF MS and Neuroinflammation Center

Uveitis

  • 38 per 100,000 persons in the U.S.
  • Mean age of onset is 30 years old
  • 50% of cases are idiopathic

Uveitis and Neurologic Disease

  • Inflammatory
  • Multiple sclerosis
  • Vogt-Koyanagi-Harada disease
  • Rheumatoid arthritis
  • Polyareteritis nodosa, ANCA vasculitis
  • Systemic lupus erythematosus
  • Sarcoidosis
  • Behcet’s disease
  • Acute posterior multifocal placoid

pigment epitheliopathy

  • Infectious
  • Viral: Herpes viruses, HIV-1, HTLV-1,

West Nile virus, measles

  • Bacterial: cat-scratch disease,

Whipple’s

  • Mycobacterial: TB, leprosy
  • Spirochetes: syphilis, Lyme,

Leptospira

  • Protozoa: toxoplasmosis,

Pneumocystis carinii

  • Nematode: gnathostomiasis,

cysticercosis

  • Neoplastic
  • Lymphoma
  • Paraneoplastic syndromes
  • Doan T, Wilson MR, Genome Med 2016

Case History: Bilateral Idiopathic Uveitis

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2/9/2017 2

  • Doan T, Wilson MR, Genome Med 2016

Bilateral Idiopathic Uveitis What is the Differential Diagnosis?

  • ?Infection
  • ?Autoimmune
  • ?Neoplastic
  • Analyzing all the genetic material in an environmental sample
  • Massively parallel sequencing approach

Metagenomic Deep Sequencing

Abbreviations: NT, nucleotide; NR, non-redundant protein.

Sequencing Library Prep

Raw Sequence (.fastq files) 19,574,979 100% Read-Pairs Retained NA NA 816,065 4.1% PriceSeqFilter v1.1.2 read-pairs 96,913 0.49% cd-hit-dup v4.6.4-2015 read-pairs 92,074 0.47% lzw-filter (script) read-pairs 2,232 0.01% bowtie2 v2.2.4 Hg38/RepBase 1,683 <0.01% gmap/gsnapl v2015-12 NCBI nt 2015 1,632,130 8.3% STAR v2.4.2 Hg38/PanTro4 RepBase Component Time (min) Target Removal of Human Reads Compression of Redundant Reads Quality Filter LZW Complexity Filter Paired-End Human Removal Alignment to nt database 1,467 <0.01% 0.0 5.8 5.9 6.3 6.9 7.4 5.2 9.3 rapsearch2 v2.23 NCBI nr 2015 9.4 MySQL v5.5.53 NCBI Taxonomy Alignment to nr database Taxnomic Stats/Reporting

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2/9/2017 3

  • Abernathy E, et al. Virology Journal 2009

Rubella virus

A

1 1000 non-synonymous synonymous 500 Coverage 100 10 1 2000 3000 4000 5000 6000 7000 8000 9000 9762 RdRp protease p150

nucleotide position E2 capsid E1

WHO

  • Abernathy E, et al. Virology Journal 2009

Substitution rates indicate active RV replication for 20 years

A

1 1000 non-synonymous synonymous 500 Coverage 100 10 1 2000 3000 4000 5000 6000 7000 8000 9000 9762 RdRp protease p150

nucleotide position E2 capsid E1

WHO

  • E1/E2 substitution rate of the patient’s RV is comparable to the documented RV

substitution rate detected from person-to-person transmission

  • Non-synonymous mutation rate in the E1 and E2 proteins was 3.4-fold higher than in the

non-structural proteins

Phylogenetic Analysis Correctly Corroborates the Time & Geographic Location of the Initial Infection

Conclusions

  • Even RNA viruses can cause chronic infections after long-term

quiescence

  • Immunosuppressed patients
  • Immune privileged body compartments
  • Public health implications for disease surveillance
  • https://www.nytimes.com/2015/05/08/health/ebola-eye-color-change-mystery.html