Sequential Occurrence of Thyroid Autoantibodies and Graves’ Disease after Immune Restoration in Severely Immunocompromised Human Immunodeficiency Virus-1-Infected Patients

Jubault, V.; Penfornis, A.; Schillo, F.; Hoën, Bruno; Izembart, M; Timsit, José; Kazatchkine, Michel D.; Gilquin, Jacques; Viard, Jean‐Paul

doi:10.1210/jcem.85.11.6988

Cited by 56 publications

(25 citation statements)

References 41 publications

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“…Multiple human connective tissue disorders are associated with lymphopenia (40)(41)(42)(43). Autoimmunity can also accompany lymphopenia caused by HIV infection (44,45), and be triggered by highly active antiretroviral therapy (46).…”

Section: Discussionmentioning

confidence: 99%

Competition for self ligands restrains homeostatic proliferation of naive CD4 T cells

Moses

Thorstenson

Jameson

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

108

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T cell antigen receptor (TCR) diversity is a critical feature of adaptive immunity. However, restriction of TCR diversity is a potential risk during immune reconstitution by homeostatic proliferation. What peripheral mechanisms are in place to maintain TCR diversity during recovery from lymphopenia? Here, we examine competition between several monoclonal CD4 T cell populations in RAG ؊/؊ and TCR Tg RAG ؊/؊ environments. The results suggest that specific self ligands constitute a critical limiting resource essential for homeostatic proliferation of naive CD4 T cells. In addition, T cells ignore large numbers of competitors as long as their TCR specificity is different and other non-MHC resources are not limiting. Therefore, the numbers of self ligands expressed in the periphery set the limits on TCR diversity.

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Section: Discussionmentioning

confidence: 99%

Competition for self ligands restrains homeostatic proliferation of naive CD4 T cells

Moses

Thorstenson

Jameson

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

108

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“…Initial presentations or exacerbations of autoimmune diseases, including systemic lupus erythematosus (SLE) [11,42], polymyositis (PM) [123] and Graves' disease [51,70,125] have been reported in patients with immune reconstitution after HAART. Cases of SLE and PM are similar to the IRD presented in Table 1, in that they occur during the first few months on HAART.…”

Section: Autoimmune Disease After Haartmentioning

confidence: 99%

“…Cases of SLE and PM are similar to the IRD presented in Table 1, in that they occur during the first few months on HAART. In contrast, Graves' disease presents after a median time of 17 months (range 9-22) after starting an initial or revised HAART regimen [70,125]. A case study of Graves' disease that presented after 2 years of HAART correlated increased thyroid stimulating hormone antibody levels with increased plasma levels of sCD30, thymic enlargement and a persistent increase in Tcell receptor rearrangement excision circle (TREC)+ CD4+ and CD8+ T-cell counts (recent thymic emigrants) and of blood naïve (CD45RA+CD62L+) T-cell counts [51].…”

Section: Autoimmune Disease After Haartmentioning

confidence: 99%

Immune Restoration Disease: A Consequence of Dysregulated Immune Responses After HAART

Stone¹,

Price²,

French

2004

CHR

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Immune Restoration Diseases (IRD) are a collection of atypical 'opportunistic infections' and inflammatory diseases seen in human immunodeficiency virus (HIV) patients after HIV viraemia is suppressed by highly active antiretroviral therapy (HAART). IRD probably reflect dysregulated immune responses against pre-existing infections by opportunistic pathogens, with different immunopathological mechanisms for different pathogens. For example, mycobacterial IRD are associated with delayed type hypersensitivity (DTH) responses to mycobacterial antigens, whereas patients who experience cytomegalovirus (CMV) IRD have elevated plasma levels of soluble CD30, a marker of a T2 cytokine environment expressed by activated CD8 T-cells. As IRD are often compartmentalised to organs, monitoring serological markers such as pathogen-specific IgG antibody, may be informative, as demonstrated for CMV and hepatitis C virus (HCV)-associated IRD. Genetic studies have provided evidence of distinct immunopathological mechanisms and inherited susceptibility to IRD associated with mycobacterial and herpesviridae infections. The expansion of HAART in the developing world where many HIV patients have low CD4+ T-cell counts and high rates of concomitant infections will place a large number of patients at-risk of developing IRD. It is therefore important to understand the immunopathology so that prevention, diagnosis and treatment can be improved.

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“…Autoimmune thyroid disease is common in patients with HIV on ART. Both Hashimoto's and Graves thyroid disease appear to occur at increased frequency, apparently reflecting an autoimmune reconstitution syndrome and occurring at variable times, 3–38 months after commencement of ART . Whilst estimates of prevalence and incidence vary, Nelson and co‐workers found a very high incidence of both subclinical and overt autoimmune hypothyroidism on cross‐sectional screening of their population of patients with HIV, higher than the predicted background rate, particularly for a predominantly younger male cohort …”

Section: Autoimmune Thyroid Dysfunctionmentioning

confidence: 99%

“…The HIV unit was concerned that he could have primary adrenal failure; however, he had no postural hypotension, weight loss, hyperpigmentation or hyperkalaemia and was less unwell than you might expect if his undetectable 9am cortisol was due to primary adrenal failure. However, this is a very reasonable thought as autoimmune endocrinopathy is well documented as part of immune reconstitution after starting antiretroviral therapy (ART), with reports particularly of autoimmune thyroid disease, but also of autoimmune diabetes although not, as yet, of autoimmune adrenal failure. Similarly, he was rather too well with a well‐preserved CD4 count and undetectable viral load to fit with a diagnosis of CMV or TB adrenalitis.…”

mentioning

confidence: 99%

How best to approach endocrine evaluation in patients with HIV in the era of combined antiretroviral therapy?

Wren

2013

Clinical Endocrinology

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SummaryEndocrine and metabolic dysfunction has been documented throughout the history of clinical experience with HIV and AIDS. Opportunistic infections such as CMV and TB adrenalitis, tumours affecting endocrine organs, and cachexia and wasting can still be seen, particulary in severely immunocompromised individuals who may be noncompliant with, resistant to, or without access to effective antiretroviral therapy (ART). However, in those with good control of their HIV infection, the profile of endocrinopathy in HIV has largely changed with the advent of highly effective combination ART. The problems that we now more frequently see in people living for many years with low viral loads and good CD4 counts relate to side effects or interactions of therapy. These included adverse metabolic effects of antiretrovirals, most notably dyslipidaemia and lipodystrophy with protease inhibitors, drug-drug interactions, including marked CYP3A4 inhibition with protease inhibitors and autoimmune endocrinopathy as part of an immune reconstitution syndrome after initiation of antiretrovirals. In addition, chronic endocrine and metabolic disorders, including hypogonadism and osteoporosis, occur at higher levels than in the background population, associated with chronic illness, lower body weight and use of both prescribed and nonprescribed drugs. To illustrate my approach to endocrine evaluation in HIV, I will describe a recent patient as the differential diagnoses considered cover the commoner endocrine complications seen. He was 34 years old, had been diagnosed with HIV 4 years previously, had regularly attended follow-up and had been started on antiretrovirals in a planned fashion 4 months previously. His antiretroviral regimen was ritonavir, darunavir and truvada (tenofovir/emtricitabine). He had a good response from an HIV point of view with undetectable viral load and improvement in his CD4 count from 319 to 382 cells/ll (normal range 300-1400) but attended his next HIV clinic appointment feeling unwell with tiredness, erectile dysfunction, loss of libido and general malaise. His thyroid function was normal, TSH 0Á59 mU/l (NR 0Á3-4Á2), fT4 15Á9 pM (NR 9-26), and he had a low testosterone 4Á5 nM, then 7Á2 nM 4 weeks later (NR 10-30 nM) with SHBG 31 nM and nonelevated gonadotrophins. Most worryingly, he had an undetectable 9am cortisol. The HIV unit rapidly arranged a short Synacthen test, which showed baseline cortisol <20 nM, 30-min cortisol of 75 nM and 60-min cortisol of 110 nM. Electrolytes were normal with potassium of 4Á0 mM.Further history in endocrine clinic revealed recent mild headaches and transient increase in appetite which had since resolved. He spontaneously volunteered that his face was fatter with fullness around his neck and weight gain, particularly around the middle. He had noted reduction in libido and erectile dysfunction with loss of morning erections over the last few months, but this was spontaneously resolving. He had some hair loss on his legs but not reduced shaving frequency. He felt tired with red...

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Sequential Occurrence of Thyroid Autoantibodies and Graves’ Disease after Immune Restoration in Severely Immunocompromised Human Immunodeficiency Virus-1-Infected Patients

Cited by 56 publications

References 41 publications

Competition for self ligands restrains homeostatic proliferation of naive CD4 T cells

Competition for self ligands restrains homeostatic proliferation of naive CD4 T cells

Immune Restoration Disease: A Consequence of Dysregulated Immune Responses After HAART

How best to approach endocrine evaluation in patients with HIV in the era of combined antiretroviral therapy?

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