# Negative Correlation Between Serum Ferritin and CD4+ Lymphocytes: A Retrospective Study on Kikuchi‐Fujimoto Disease

## TL;DR

This study found that higher ferritin levels in Kikuchi–Fujimoto disease are linked to lower CD4+ lymphocyte counts, suggesting immune system disruption.

## Contribution

The study reveals a novel negative correlation between serum ferritin and CD4+ lymphocytes in Kikuchi–Fujimoto disease.

## Key findings

- KFD patients with high ferritin had significantly lower CD4+ lymphocyte counts and percentages.
- Serum ferritin levels showed a strong negative correlation with CD4+ lymphocyte counts and percentages.
- Biopsied lymph nodes were primarily located in the neck with specific size measurements.

## Abstract

Kikuchi–Fujimoto disease (KFD) is a rare condition characterized by elevated serum ferritin levels and a robust immune response involving various lymphocyte subtypes. However, the relationship between ferritin and lymphocyte subtypes remains unexplored. This study aims to offer insights into the immune response in KFD.

Sixty‐five hospitalized patients diagnosed with KFD through histopathological examination were categorized into hyperferritinemia and control groups. Baseline characteristics, ultrasound findings, and laboratory results were retrospectively collected for analysis.

Biopsied lymph nodes in KFD patients were predominantly located in the neck (89.2%), followed by the axilla (6.2%) and submandible (4.6%). These nodes exhibited a mean long diameter of 2.3 mm (interquartile range [IQR] 2.0–2.8 mm) and a mean short diameter of 0.9 mm (IQR 0.7–1.2 mm). A comparison between the hyperferritinemia and control groups revealed significant differences: Serum ferritin levels were 664.4 µg/L (IQR 450.5–963.9 µg/L) vs. 111.3 µg/L (IQR 75.7–207.4 µg/L), respectively. Additionally, counts of CD3+ and CD4+ lymphocytes, as well as NK cells, were reduced in the hyperferritinemia group: CD4+ lymphocyte counts were 387.7 cells/µL (IQR 261.5–479.7 cells/µL) vs. 479.9 cells/µL (IQR 396.2–662.0 cells/µL), p = 0.021; and the percentage of CD4+ lymphocytes was 33.8% (IQR 29.4‐41.7%) vs. 42.4% (IQR 40.4–48.6%), p = 0.000. Furthermore, serum ferritin levels exhibited a linear positive correlation with CRP (r = 0.420, p = 0.001) and a negative correlation with CD4+ lymphocyte count (r = −0.412, p = 0.007) and percentage of CD4+ lymphocytes (r = −0.567, p = 0.000).

Patients with KFD demonstrated immunosuppression characterized by decreased counts of circulating CD3+ and CD4+ lymphocytes, as well as NK cells. Moreover, serum ferritin levels were inversely correlated with CD4+ lymphocyte counts, suggesting a potential role of ferritin in immune dysregulation in KFD.

This retrospective cohort study indicates that patients with Kikuchi–Fujimoto disease demonstrated immunosuppression characterized by decreased counts of circulating CD3+ and CD4+ lymphocytes. Moreover, serum ferritin levels were inversely correlated with CD4+ lymphocyte counts, suggesting a potential role of ferritin in immune dysregulation in Kikuchi–Fujimoto disease.