Slides from a Microsoft PowerPoint presentation delivered by Jackson David Reynolds on March 30, 2017 for the Immunology (BIOL 4100) course of Dr. Chuck Fink, PhD at Dalton State College in Dalton, GA, USA.

1. Jackson David Reynolds, BS,AS
Dalton State College
Kaposi Sarcoma
in
Immune Reconstitution Inflammatory Syndrome
Figures (clockwise) from: Lavigne et al.,1998; Dalton State College &VisionPoint Marketing, 2016; Kelley L.A., et al., 2015. 1

2. Kaposi Sarcoma (KS) & HIV/AIDS
• Human Herpesvirus type 8 (HHV-8)
• Kaposi Sarcoma associated Herpesvirus (KSHV)
• Immunodeficiency
• Endothelial cells
• Latent/lysogenic
• Tumors expansion = angiogenesis
American Cancer Society, Inc., 2016. Figures (clockwise) modified from: Henderson & Physicians Research Network (PRN®), 2002; National Cancer Institute,
2001; Silverman, Jr. & Centers for Disease Control and Prevention Public Health Image Library (PHIL), 1999.
2

3. Cytoplasm Nucleus
KSHV Engenders Angiogenesis via Activation
of Proinflammatory Cascades.
Chang et al., 2016. Figure modified from: Chang et al., 2016.
NOTTOSCALE
= miR-221/-222 promoter
= cytokine transcripts
Kaposin
B
c-myc
KSHV
∴ ↑[cytokines]cytosolANGIOGENESIS
= miR-221/-222
3

4. Highly Active Antiretroviral Therapy (HAART)
• Multi-drug approach
• Longitudinal treatment
• Very effective
• Mortality: >30% à <9%
Collier et al., 1996; National Institute on Drug Abuse, 2012; Palella et al., 1998; Riying et al., 2017; Shafer &Vuitton, 1999. Figure from: Splettstoesser, 2013.
4

5. Immune Reconstitution Inflammatory Syndrome (IRIS)
• Iatrogenic (2º to HAART)
• CD4+ count rapidly increases
• Occult infections suddenly
become violently symptomatic
• Severity of symptoms likely*
the result of an Ag-specific T-
cell mediated response to
occult pathogens
*Detailed MOA not yet entirely elucidated…
Bosamiya, 2011; Kiggundu, Nabeta, Okia, Rhein, & Lukande, 2016; Sharma & Soneja, 2011. Figure modified from: Kiggundu, Nabeta, Okia, Rhein, & Lukande,
2016.
5

6. IRIS in the Context of KS
• Rare
• Atypical presentation of KS
• Pleuropulmonary
• Can be rapidly fatal
Bower et al., 2005; Odongo, 2013; Suresh, Semaan, Arias, Karakousis, & Lee, 2016. Figures modified from: (left & middle) Suresh, Semaan, Arias, Karakousis,
& Lee, 2016; (right) Odongo, 2013.
6

7. IRIS, Statins, & (Possible?) KS Prophylaxis
Drechsler et al., 2017. 7

8. American Cancer Society, Inc. (2016, February 9). Kaposi Sarcoma. Retrieved February 21, 2017, from
http://www.cancer.org/cancer/kaposisarcoma/ detailedguide/kaposi-sarcoma-what-is-key-statistics
Bosamiya, S. (2011).The immune reconstitution inflammatory syndrome. Indian Journal of
Dermatology, 56(5), 476. doi:10.4103/0019-5154.87114
Bower, M., Nelson, M.,Young,A. M.,Thirlwell, C., Newsom-Davis,T., Mandalia, S., . . . Stebbing, J. (2005).
Immune reconstitution inflammatory syndrome associated with Kaposi's sarcoma. Journal of Clinical
Oncology, 23(22), 5224-5228. Retrieved March 6, 2017.
Chang, H., Hsieh,T., Lee,Y.,Tsai, C.,Tsai,Y., Cheng, C., &Wang, H. (2016). C-Myc and viral cofactor
Kaposin B co-operate to elicit angiogenesis through modulating miRNome traits of endothelial cells.
BMC Systems Biology, 10(S1). doi:10.1186/s12918-015-0242-3
Collier,A. C., Coombs, R.W., Schoenfeld, D.A., Bassett, R. L.,Timpone, J., Baruch,A., . . . Corey, L.
(1996).Treatment of Human ImmunodeficiencyVirus Infection with Saquinavir, Zidovudine, and
Zalcitabine. New England Journal of Medicine, 334(16), 1011-1018. doi:10.1056/nejm199604183341602
Dalton State College, &VisionPoint Marketing. (2016). Dalton state logo [Digital image]. Retrieved
February 20, 2017, from https://www.daltonstate.edu/skins/userfiles/files/2016-7-
27%20DaltonState_BrandGuidelines.pdf
References I
8

9. Drechsler, H.,Ayers, C., Cutrell, J., Maalouf, N.,Tebas, P., & Bedimo, R. (2017). Current use of statins
reduces risk of HIV rebound on suppressive HAART. Plos One, 12(3).
doi:10.1371/journal.pone.0172175
Henderson, L. E., PhD, & Physicians Research Network (PRN®). (2002, March). Kaposi’s sarcoma-
associated herpesvirus (KSHV), or human herpesvirus-8 (HHV-8), in saliva [Digital image]. Retrieved
February 27, 2016, from http://www.prn.org/images/uploads/ kshv_hhv-8_in_saliva_1200_800.jpg
Kiggundu, R., Nabeta, H.W., Okia, R., & Rhein, J. (2016, December 30). Cutaneous lesions throughout
on the face before the antifungal treatment. [Digital image]. Retrieved March 6, 2017, from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304559/figure/g01/
Kiggundu, R., Nabeta, H.W., Okia, R., Rhein, J., & Lukande, R. (2016). Unmasking histoplasmosis
immune reconstitution inflammatory syndrome in a patient recently started on antiretroviral
therapy. Autopsy and Case Reports, 6(4), 27-33. doi:10.4322/acr.2016.048
Lavigne, P., Crump, M. P., Hodges, R. S., Kay, C. M., Sykes, B. D., & Gagné, S. M. (1998). Insights into the
mechanism of heterodimerization from the 1H-NMR solution structure of the c-Myc-Max
heterodimeric leucine zipper. Journal of Molecular Biology, 281(1), 165-181.
doi:10.1006/jmbi.1998.1914
References II
9

10. National Cancer Institute. (2001, January 1). Kaposi's sarcoma [Kaposi's sarcoma on the skin of an
AIDS patient.]. Retrieved February 27, 2016, from https://visualsonline.cancer.gov/
details.cfm?imageid=2168
National Institute on Drug Abuse. (2012, July).What is HAART? Retrieved March 6, 2017, from
https://www.drugabuse.gov/publications/research-reports/hivaids/what-haart
Odongo, F. C. (2013). Fatal disseminated Kaposi's sarcoma due to immune reconstitution
inflammatory syndrome following HAART initiation. Case Reports in Infectious Diseases, 2013, 1-3.
doi:10.1155/2013/546578
Odongo, F. C. (2013). Figure 2 [Initial chest CT scan at the ICU, revealing bilateral patchy infiltrates
suggestive of lung KS or alveolar hemorrhage.]. Retrieved March 6, 2017, from
https://www.hindawi.com/journals/criid/2013/546578/fig2/
Palella, F. J., Delaney, K. M., Moorman,A. C., Loveless, M. O., Fuhrer, J., Satten, G.A., . . . Holmberg, S. D.
(1998). Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency
Virus Infection. New England Journal of Medicine, 338(13), 853-860.
doi:10.1056/nejm199803263381301
Riying, L., Guojian, L., Jizhou,W.,Yujia, Z., Jianlong, L., Xionglin, Q., . . . Chaoyu, X. (2017). Investigation
of the survival time and quantification of therapeutic benefits for HIV patients with highly active
antiretroviral therapy. Biomedical Research, 28(1), 279-283. Retrieved February 21, 2017.
References III
10

11. Shafer, R.W., &Vuitton, D.A. (1999). Highly active antiretroviral therapy (Haart) for the treatment of
infection with human immunodeficiency virus type 1. Biomedicine & Pharmacotherapy, 53(2), 73-86.
doi:10.1016/s0753-3322(99)80063-8
Sharma, S., & Soneja, M. (2011). HIV & immune reconstitution inflammatory syndrome (IRIS). The
Indian Journal of Medical Research, 134(6), 866-877. doi:10.4103/0971-5916.92632
Silverman, S., Jr., DDS, & Centers for Disease Control and Prevention Public Health Image Library
(PHIL). (1999). Kaposi sarcoma of the mouth [This HIV-positive patient presented with an intraoral
Kaposi’s sarcoma lesion with an overlying candidiasis infection.]. Retrieved February 27, 2016, from
http://phil.cdc.gov/phil_images/ 20040819/5/072_lores.jpg
Splettstoesser,T. (2013, November 6). HIV-drug-classes [Schematic description of the mechanism of
the four classes of currently available antiviral drugs against HIV: fusion inhibitors ( interfere with the
binding, fusion or entry of an HIV virion), reverse-transcriptase inhibitors (interfere with the
translation of viral RNA into DNA), integrase inhibitors (block the viral enzyme integrase, that
inserts the viral genome into the DNA of the host cell), protease inhibitors (block proteolytic
cleavage of protein precursors that are necessary for the production of infectious viral particles)].
Retrieved February 21, 2017, from https://commons.wikimedia.org/wiki/File:HIV-drug-classes.svg
References IV
11

12. Suresh, K., Semaan, R.,Arias, S., Karakousis, P., & Lee, H. (2016, May 30). Figure 1 [Pleural KS lesions.].
Retrieved March 6, 2017, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943458/figure/F1/
Suresh, K., Semaan, R.,Arias, S., Karakousis, P., & Lee, H. (2016). Pleuropulmonary Kaposi sarcoma in
the setting of immune reactivation. Journal of Pulmonary & Respiratory Medicine, 6(3).
doi:10.4172/2161-105x.1000352
Vanable, P.A., Ostrow, D. G., Mckirnan, D. J.,Taywaditep, K. J., & Hope, B.A. (2000). Impact of
combination therapies on HIV risk perceptions and sexual risk among HIV-positive and HIV-negative
gay and bisexual men. Health Psychology, 19(2), 134-145. doi:10.1037//0278-6133.19.2.134
ReferencesV
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