Circulating Soluble Factors and T-Cell Subsets as Immunological Predictors of Therapy Response in Human Cutaneous Leishmaniasis - Scorecard - MDSpire

Circulating Soluble Factors and T-Cell Subsets as Immunological Predictors of Therapy Response in Human Cutaneous Leishmaniasis

  • By

  • Amanda B Figueiredo

  • Katia L P Morais

  • Israel T Silva

  • Lorhenn B L Maia

  • Jaqueline R Buttura

  • Bruna D F Barros

  • Natalia S Alves

  • Flavio Pignataro-Oshiro

  • Samara M M Shimon

  • Andrea Teixeira-Carvalho

  • Lucas Almeida

  • Edgar Carvalho

  • Paulo Machado

  • Jenefer M Blackwell

  • Lea Castellucci

  • Walderez O Dutra

  • Kenneth J Gollob

  • February 4, 2025

  • 0 min

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Clinical Scorecard: Immunological Indicators of Treatment Response in Human Cutaneous Leishmaniasis: The Role of Circulating Soluble Factors and T-Cell Subpopulations

At a Glance

CategoryDetail
ConditionHuman cutaneous leishmaniasis caused by Leishmania braziliensis
Key MechanismsHost–parasite immune interactions involving cytokine balance and T-cell subsets, notably CD8+ MAIT cells influencing pathology and treatment response
Target PopulationPatients with active cutaneous leishmaniasis in endemic regions, specifically from Corte de Pedra, Bahia, Brazil
Care SettingClinical management in tropical disease endemic areas with laboratory and immunological diagnostic support

Key Highlights

  • Circulating soluble factors in plasma serve as promising noninvasive predictive markers for treatment outcomes in human CL.
  • Elevated frequencies of circulating and lesion-associated CD8+ mucosal-associated invariant T (MAIT) cells correlate with increased lesion pathology and refractory response to therapy.
  • Combination of immunological signatures including cytokine profiles and T-cell subpopulations can guide tailored immunomodulatory interventions to improve treatment efficacy.

Guideline-Based Recommendations

Diagnosis

  • Diagnosis based on clinical presentation of ulcerated lesions, positive skin Montenegro test, parasite isolation, and histopathological confirmation.
  • Species typing to confirm Leishmania braziliensis infection.

Management

  • First-line treatment with meglumine antimoniate at 20 mg/kg/day for 20 days.
  • Consider alternative therapies such as miltefosine, pentoxifylline, or granulocyte colony-stimulating factor in cases of antimonial failure or adverse effects.
  • Use of antimonials combined with immunomodulatory drugs in severe or refractory cases.

Monitoring & Follow-up

  • Evaluate treatment response at 60 days post-therapy by assessing lesion reepithelialization.
  • Monitor immunological markers including circulating soluble factors and CD8+ MAIT cell frequencies to predict and assess treatment efficacy.

Risks

  • Potential for treatment failure and drug resistance with standard therapies.
  • Risk of disease progression to severe mucosal involvement if unresponsive to treatment.

Patient & Prescribing Data

265 patients with active cutaneous leishmaniasis; 126 responders and 139 refractory after 60 days of meglumine antimoniate therapy.

Standard meglumine antimoniate therapy shows variable efficacy; immunological profiling may identify patients at risk of treatment failure to guide alternative or adjunctive therapies.

Clinical Best Practices

  • Employ multiparametric flow cytometry and RNA sequencing to assess immunological markers pre-therapy.
  • Incorporate noninvasive plasma soluble factor analysis for early prediction of treatment response.
  • Tailor therapeutic strategies based on immunological profiles, especially targeting CD8+ MAIT cell-associated pathways in refractory patients.
  • Ensure comprehensive clinical and laboratory diagnosis including species confirmation before treatment initiation.
  • Follow patients closely for at least 60 days post-treatment to evaluate lesion healing and adjust management accordingly.

References

Original Source(s)

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