Graves' disease as immune reconstitution disease in HIV-positive patients is associated with naive and primary thymic emigrant CD4(+) T-cell recovery.
OBJECTIVE
Immune restoration disease (IRD) can develop in HIV-infected patients following antiretroviral therapy (ART) initiation as unmasking or paradoxical worsening of opportunistic infections and, rarely, autoimmune phenomena. Although IRD usually occurs in the first months of ART during memory CD4 T-cell recovery, Graves' disease occurs as a distinctive late-onset IRD and its pathogenesis is unclear.


METHODS
Seven patients who developed Graves' disease following ART initiation from the primary HIV care clinic at the National Institutes of Health were retrospectively identified and each was matched with two HIV-infected controls based on age, sex, and baseline CD4 T-cell count. Laboratory evaluations on stored cryopreserved samples were performed.


METHODS
Immunophenotyping of peripheral blood mononuclear cells (PBMCs), T-cell receptor excision circle (TREC) analysis in PBMCs, measurement of serum cytokines, and luciferase immunoprecipitation systems (LIPS) analysis for autoimmune antibodies were performed on stored samples for cases and controls at baseline and longitudinally following ART initiation. TSH/thyrotropin receptor (TSH-R) antibody testing was performed on serum from cases. Data were analyzed using nonparametric testing.


RESULTS
In comparison with controls, the proportion of naive CD4 T cells increased significantly (P = 0.0027) in the Graves' disease-IRD patients. TREC/10 PBMCs also increased significantly following ART in Graves' disease-IRD patients compared with controls (P = 0.0071). Similarly, LIPS analysis demonstrated increases in nonthyroid-related autoantibody titers over time following ART in cases compared with controls.


CONCLUSIONS
Our data suggest that Graves' disease-IRD, in contrast to early-onset IRD, is associated with naive and primary thymic emigrant CD4 T-cell recovery and inappropriate autoantibody production.
aNational Institute of Allergy and Infectious Diseases (NIAID) bBiostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda cScience Applications International Corporation-Frederick, Frederick National Laboratory, Frederick dClinical Dental Research Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
Virginia
V
Sheikh
Rebecca
R
Dersimonian
Aaron G
AG
Richterman
Brian O
BO
Porter
Ven
V
Natarajan
Peter D
PD
Burbelo
Adam
A
Rupert
Brian H
BH
Santich
Lela
L
Kardava
JoAnn M
JM
Mican
Susan
S
Moir
Irini
I
Sereti
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D006111:Graves Disease / Q000276:immunology* / Q000473:pathology; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000276:immunology* / Q000473:pathology; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
D044966:Anti-Retroviral Agents; D001323:Autoantibodies; D016207:Cytokines