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Could different aqueous humor and plasma cytokine profiles help differentiate between ocular sarcoidosis and ocular tuberculosis?

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Abstract

Objective and design

A cross-sectional single-center study was conducted to assess cytokine levels in aqueous humor (AH) and plasma of three different uveitis entities: definite ocular sarcoidosis (OS), definite OS associated with QuantiFERON®-TB Gold test positivity (Q + OS) and presumed tubercular uveitis (TBU).

Subjects

Thirty-two patients (15 OS, 5 Q + OS, 12 TBU) were included.

Methods

Quantification of selected cytokines was performed on blood and AH samples collected before starting any treatment. Statistical analysis was conducted using the Kruskal–Wallis test, the Mann–Whitney or Fisher test and the Principal Component Analysis (PCA).

Results

IL-6, IL-8 and IP-10 levels were higher in AH samples than in peripheral blood. In AH samples, BLC, IL-8 and IP-10 were significantly higher in definite OS than in presumptive TBU. There were no statistically significant differences in terms of cytokine levels between Q + OS and presumptive TBU. PCA showed a similar cytokine pattern in the latter two groups (IFNγ, IL-15, IL-2, IP-10, MIG), while the prevalent expression of BLC, IL-10 and MIP-3 α was seen in definite OS.

Conclusions

The different AH and plasma cytokine profiles observed in OS compared to Q + OS and TBU may help to differentiate OS from TBU in overlapping clinical phenotypes of granulomatous uveitis (Q + OS).

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Acknowledgements

Thanks to Jacqueline M. Costa for the English language editing.

Author information

Author notes

  1. L. De Simone and M. Bonacini contributed equally to this work.

  2. S. Croci and L. Cimino these senior authors contributed equally to this work.

Authors and Affiliations

  1. Ocular Immunology Unit, Azienda USL-IRCCS, Reggio Emilia, Italy

    L. De Simone, V. Mastrofilippo, F. Gozzi, E. Bolletta, C. Adani & L. Cimino

  2. Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS, Reggio Emilia, Italy

    M. Bonacini, A. Zerbini & S. Croci

  3. Department of Medicine and Surgery, University of Parma, Parma, Italy

    R. Aldigeri

  4. Department of Biomedical Sciences, Ophthalmology Clinic, University Hospital of Messina, Messina, Italy

    F. Alessandrello

  5. Ocular Immunology Unit, Department of Surgery, Medicine, Dentistry and Morphological Sciences, with Interest in Transplants, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Azienda USL-IRCCS Di Reggio Emilia, 42121, Reggio Emilia, Modena, Italy

    G. M. Cavallini, C. Salvarani & L. Cimino

  6. Ophthalmology Unit, DIMES, Alma Mater Studiorum, University of Bologna and S.Orsola-Malpighi Teaching Hospital, Bologna, Italy

    L. Fontana

  7. Division of Rheumatology, Azienda USL-IRCCS, Reggio Emilia, Italy

    C. Salvarani

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  1. L. De Simone
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Contributions

LDS, EB, FG, and LC recruited the patients. MB and SC performed cytokine and immune cell profiling. LDS, MB, VM, FG, EB, CA, SC and LC contributed to the writing of the protocol and researched data. RA performed the statistical analysis. LDS, MB, RA, FA, SC and LC drafted the manuscript. LDS, MB, RA, FA, FG, EB, AZ, LF, CS, SC and LC interpreted the data and critically revised the manuscript. LC is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to L. Cimino.

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Supplementary Information

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11_2022_1601_MOESM1_ESM.tif

Fig. Supplementary 1 FACS gating strategy. Gating strategy used to quantify lymphocytes, monocytes and neutrophils and CD4 + , CD8 + T cells, NK cells, NKT cells and B lymphocytes. (TIF 15113 KB)

11_2022_1601_MOESM2_ESM.tif

Fig. Supplementary 2 Leukocyte subsets in AH samples. A Leucocyte concentrations evaluated by manual counting with a Neubauer hemocytometer; B) Percentages of NK (CD56 + CD3neg), NKT (CD56 + CD3 +), B (CD19 + CD3neg), T (CD56negCD3 +), CD4T (CD56negCD3 + CD4 +) and CD8T (CD56negCD3 + CD8 +) cells; C) Ratio between the percentages of CD4 + and CD8 + T cells in AH samples from patients classified as OS (red dots), Q + OS (blue dots) and TBU (green dots). Horizontal lines show the median ± interquartile range (IQR). Data were analysed by Mann–Whitney test. (TIF 110 KB)

11_2022_1601_MOESM3_ESM.tif

Fig. Supplementary 3 Cytokine concentration in plasma samples. Heatmap of cytokine levels in plasma samples from each patient obtained with ClustVis software. B) Cytokine concentrations (pg/ml) detected in plasma samples from patients classified as OS (red dots), Q + OS (blue dots) and TBU (green dots). Plasma samples from control subjects (CTR) were used as reference. Horizontal lines show the median ± interquartile range (IQR). Data were analysed by Mann–Whitney test. No comparisons reached statistical significance, set ts p < 0.05. Dashed line shows the detection limit for each cytokine. (TIF 146 KB)

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De Simone, L., Bonacini, M., Aldigeri, R. et al. Could different aqueous humor and plasma cytokine profiles help differentiate between ocular sarcoidosis and ocular tuberculosis?. Inflamm. Res. 71, 949–961 (2022). https://doi.org/10.1007/s00011-022-01601-2

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