Serum Immune Proteins in Limb Lymphedema Reflecting Tissue Processes Caused by Lymph Stasis and Chronic Dermatolymphangioadenitis (Cellulitis)

Marzanna T. Zaleska and Waldemar L. Olszewski, Lymphatic Research and Biology 2017

Click to read the abstract

Abstract

Serum Immune Proteins in Limb Lymphedema Reflecting Tissue Processes Caused by Lymph Stasis and Chronic Dermatolymphangioadenitis (Cellulitis)

Marzanna T. Zaleska and Waldemar L. Olszewski, Lymphatic Research and Biology 2017

Background: Lymphedema of limbs affects a large mass of tissues. Pathological changes develop in skin and subcutaneous tissue. Bacterial retention in edema fluid is followed by chronic inflammatory reaction. The question arises whether the chronic processes affecting a large mass of limb tissues are reflected in the serum by appearance of specific proteins accumulating and subsequently absorbed from the lymphedematous tissues

Aim: To measure the concentration of serum proteins (1) participating in cellular disintegration such as caspase 1, sFas, high-mobility group box 1 (HMGB1), and serpin, (2) cell growth regulating factors such as cortisol, human growth hormone, keratinocyte growth factor, and insulin-like growth factor (IGF), and (3) angiogenic and growth factors such as angiopoetins 1 and 2, adiponectin, leptin, and transforming growth factor beta.

Results: We found (1) increased concentration of serum caspase 1, sFas, serpin, and HMGB1 accounting for cellular destruction, (2) raised levels of cortisol and IGF, confirming active cellular processes, and (3) elevated concentrations of angiopoetin 1, adiponectin, and leptin, indicating proliferation of adipose tissue.

Conclusions: Proteins appearing in serum in high concentrations in patients with lymphedema without systemic clinical and biochemical signs of inflammation indicate that multiple processes of destruction and rebuilding proceed in the lymphedematous tissues. Measuring concentration of caspase 1, sFas, serpin, HMGB1 protein, adiponectin, and leptin give insight into these processes. Lymphedema should be considered as tissue process characterized not only by increase in mobile tissue fluid volume but also tissue restructuring. Compression and drainage therapy should be complemented by anti-inflammatory medication.

Main findings

  • One hundred patients aged 21–62 were included. Lymphoedema of the lower limbs stages II to IV of >3 years duration. There were 55 females and 45 males. Their body mass index (BMI) was <26kg/m2. They underwent screening for identification of lymphatic obstruction. The initial etiology of lymphedema was soft bacterial tissue inflammation in calf or foot with a latent period of months or years of no edema. Edema appeared either spontaneously or after a minor trauma.
  • Inclusion criteria were lower limbs swelling after foot or calf dermatitis with at least three episodes of acute dermato-lymphangio-adenitis (DLA) and recent in the past 12 months.
  • Lymphoedema was confirmed via clinical evaluation, lymphoscintigraphic evaluation and fluorescent lymphography evaluation.
  • The protein concentration data from lymphedema patients were compared with those obtained from studies in normal subjects.
  • Group 1: proteins released from tissues with inflammatory reaction was increased approximately twice compared with normal.
  • Group 2: hormones regulating tissue reconstruction. Serum cortisol level was slightly elevated, whereas the insulin-like GF level was four times higher.
  • Group 3: hormones participating in fibrous and adipose tissue growth were increased by a factor of 2.
  • Lymphedema should be considered as tissue process characterized by not only increase in mobile tissue fluid volume but also tissue restructuring. Compression and drainage therapy should be complemented by anti-inflammatory medication.