Dynamics of plasma micronutrient concentrations and their correlation with serum proteins and thyroid hormones in patients with paracoccidioidomycosis.

Jeniffer Michelline de Oliveira Custódio,Iasmim Mayumi Enokida,Sandra Maria do Valle Leone de Oliveira,Anamaria Mello Miranda Paniago,Lidia Raquel Carvalho,Rinaldo Poncio Mendes,Daniel Araujo Gonçalves,James Venturini,Creuza Rachel Vicente

doi:10.1371/journal.pone.0226609

Jeniffer Michelline de Oliveira Custódio, Iasmim Mayumi Enokida + Show 7 more

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https://doi.org/10.1371/journal.pone.0226609

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Abstract

Minerals, such as zinc, copper, and iron are reported to play roles in chronic infectious diseases; however, their role in paracoccidioidomycosis (PCM) remains unknown. This study aimed to examine the micronutrient dynamics and their correlation with serum proteins and thyroid hormones in patients with PCM. In 14 patients with PCM and 10 healthy subjects, we evaluated the body mass index (BMI) along with serum levels of hemoglobin, iron, ferritin, zinc, copper, magnesium, albumin, globulin, thyroid stimulating hormone (TSH), thyroxine (free T4), and triiodothyronine (T3). Evaluations were conducted at the first appointment, before treatment, and at the end of the first, second, fourth, and sixth month of PCM treatment. The control group was only evaluated once. We observed that before treatment, patients with PCM, had higher levels of copper and lower level of iron than those of the control group. After one month of treatment, the iron levels increased, whereas the levels of copper after six months of treatment. Reduction in inflammatory activity, indicated by the normalization of C-reactive protein, ferritin, albumin, and globulin levels, was observed during treatment. However, no correlation was observed between the serum levels of minerals and inflammatory activity or thyroid function in this study. In conclusion, our results showed higher serum copper levels in control group compared to those in pretreatment patients; the clinical importance of this observation should be investigated in further studies. After treatment, serum copper levels showed a tendency to decrease. In addition, serum iron levels were decreased at the stage of active disease, and were increased after treatment. Thus, serum iron levels can be used as a better biomarker for treatment control.

Highlights

Paracoccidioidomycosis (PCM), caused by fungi of the genus Paracoccidioides, is a systemic mycosis endemic to Latin America
We considered moderate if the lymph nodes enlargement was inflammatory, non-suppurative; hepatomegaly/ splenomegaly were absent or mild; body mass index (BMI) loss lower than 10%; and low antibody titers
IQR: interquartile range, BMI: body mass index in Kg/m2, UADT: upper air digestive tract, CNS: Central Nervous System. # Between onset of symptoms and PCM diagnosis. ## One patient could have more than one affected organ Mann Whitney U test for the comparison of numerical variables and Fisher for comparison of categorical variables

Summary

Introduction

Paracoccidioidomycosis (PCM), caused by fungi of the genus Paracoccidioides, is a systemic mycosis endemic to Latin America. Similar to bacteria and humans, fungi require an adequate concentration of trace metals for sufficient cellular functioning, including respiration, replication, transcription, translation, and regulation of virulence [1, 2]. The mechanisms by which defense cells control the invasion of microorganisms involve the redistribution of essential trace elements such as zinc, copper, and iron in serum, as well as increased synthesis of acute phase proteins such as ceruloplasmin. These changes are mediated by tumor necrosis factor α (TNF-α) as well as interleukin-1 (IL-1), and interleukin-6 (IL-6) [3]. Metal acquisition systems import and remove metals from extracellular sites using siderophores and acquisition of host proteins [1, 4, 5]

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