Objectives During periodontitis, chronic inflammation triggers soft tissue breakdown, and hyaluronan is degraded into fragments
of low molecular weight (LMW-HA). This investigation aimed to elucidate whether LMW-HA fragments with immunogenic
potential on T lymphocytes remain in periodontal tissues after periodontal treatment.
Materials and methods GCF samples were obtained from 15 periodontitis-affected patients and the LMW-HA, RANKL, and
OPG levels were analyzed before and after 6 months of periodontal treatment by ELISA. Eight healthy individuals were analyzed
as controls. Besides, human T lymphocytes were purified, exposed to infected dendritic cells, and pulsed with LMW-HA. Nontreated T lymphocytes were used as control. The expression levels of the transcription factors and cytokines that determine the
Th1, Th17, and Th22 lymphocyte differentiation and function were analyzed by RT-qPCR. Similarly, the expression levels of
RANKL and CD44 were analyzed.
Results In the GCF samples of periodontitis-affected patients, higher levels of LMW-HA were detected when compared with
those of healthy individuals (52.1 ± 15.4 vs. 21.4 ± 12.2, p < 0.001), and these increased levels did not decrease after periodontal
therapy (52.1 ± 15.4 vs. 45.7 ± 15.9, p = 0.158). Similarly, the RANKL levels and RANKL/OPG ratios did not change after
periodontal therapy. Furthermore, in human T lymphocytes, LMW-HA induced higher expression levels of the Th1, Th17, and
Th22-related transcription factors and cytokines, as well as CD44 and RANKL, as compared with non-treated cells.
Conclusions In some patients, increased levels of LMW-HA persist in periodontal tissues after conventional periodontal therapy,
and these remaining LMW-HA fragments with immunostimulatory potential could induce the polarization of a pathologic Th1/
Th17/Th22-pattern of immune response on T lymphocytes.
Clinical relevance The persistence of increased levels of LMW-HA in periodontal tissues after periodontal therapy could favor
the recurrence of the disease and further breakdown of periodontal supporting tissues
