Abstract
Background
Up to 20% of patients are dissatisfied following TKA, most often due to pain and/or stiffness. The differential diagnosis includes an immune reaction to the prosthesis. However, there is no consensus on diagnostic criteria for immune failure, an allergic reaction, to a TKA.
Histologic evaluation could provide evidence as to whether an allergic reaction caused TKA failure. A recent study showed an increase in CD4+ lymphocytes compared to CD8+ lymphocytes in patients LTT+ for Ni. This finding is consistent with Ni sensitization, but can lymphocyte subsets be used to diagnose immune failure on a case-by-case basis?
Methods
Periprosthetic tissues from 18 revision cases of well-fixed, aseptic, but painful and/or stiff primary TKAs were analyzed. Six patients LTT− for Ni were matched as a cohort for age, sex, and BMI, to 12 patients LTT+ for Ni. Periprosthetic tissue biopsies underwent IHC staining for CD4+ and CD8+ lymphocyte subsets and were compared by LTT status. The IHC results were also compared with periprosthetic histology.
Results
There was no relationship between LTT status and mean CD4+ cells/hpf or CD4+:CD8+ lymphocyte ratio. No relationship was found between LTT stimulation index (continuous or categorical) and CD4+:CD8+ ratio or ALVAL score.
Conclusion
Lymphocytes in periprosthetic tissue are highly variable in number, subtype ratio, and location, and have no relationship to LTT result or ALVAL score on a case-by-case basis. Based on these results, lymphocyte subsets cannot diagnosis immune failure. Further work is needed to determine criteria for the diagnosis of immune failure of a TKA.
Keywords: total knee arthroplasty, TKA, revision total knee arthroplasty, metal hypersensitivity, metal allergy in arthroplasty, immune mediated TKA failure
Introduction
Up to 20% of patients are dissatisfied following total knee arthroplasty (TKA), most often due to residual pain and/or stiffness.1-3 The differential diagnosis includes an immune reaction to the prosthesis. However, there is no consensus on diagnostic criteria for immune failure, an allergic reaction, to a total knee arthroplasty (TKA).4
There is an increasing portion of the population with metal sensitivity, most commonly to Ni. Up to 60% of patients with a failed TKA are sensitized to Ni.5 Unfortunately, skin patch testing has no prognostic utility in TKA.6 Lymphocyte transformation testing (LTT) has also been used to diagnosis metal sensitivity. LTT is an in-vitro quantitative assay that exposes lymphocytes, extracted from a whole blood sample to relevant antigens (i.e., nickel) and then measures their reaction, or stimulation, determining to what degree the patient has been sensitized to the antigen in question. However, the prognostic utility of LTT in predicting TKA outcomes has not been determined. Further, LTT results are not associated with TKA outcomes or periprosthetic histology as graded by the “aseptic lymphocyte-dominant vasculitis-associated lesion” (ALVAL) scoring system.7-9
Lionberger et al. reported an increase in CD4+lymphocytes in periprosthetic histological section in revision TKA patients LTT+ for Ni.10 This finding is consistent with Ni sensitization, but can lymphocyte subsets be used to diagnose immune failure on a case-by-case basis? The goal of this study is to determine if periprosthetic lymphocyte subsets can be used to diagnose an immune reaction in a painful and/or stiff TKA by examining the following questions:
Is there a relationship between LTT status and periprosthetic CD4+ cells per high powered field (cells/hpf), CD8+ cells/hpf, or CD4+:CD8+ lymphocyte ratio?
Is there any correlation between LTT stimulation index (SI) and periprosthetic lymphocyte ratio?
Is there an association between LTT SI reactivity (mild, moderate, and highly reactive) and periprosthetic lymphocyte ratio?
Is there any correlation between ALVAL score and periprosthetic lymphocyte ratio?
Material and Methods
Institutional review board approval was obtained to perform a retrospective review of revision TKAs from a single surgeon’s practice. Inclusion criteria were subjects who previously had a TKA procedure and had complaints of chronic knee pain, with a negative infection workup, no radiographic evidence of loosening, had a positive intra-articular lidocaine/bupivacaine diagnostic challenge, and had LTT results prior to undergoing revision. Infection work-up was performed in accordance with Musculoskeletal Infection Society (MSIS) recommendations.11
Patient Selection
The selection of study participants was described previously by Schneiderman et al.9 Briefly, in a single surgeon series, 56 patients undergoing revision cemented knee arthroplasty met the above inclusion criteria. Of these, we included all 6 LTT− patients and 12 LTT+patients matched to the LTT− group for age, sex, and body mass index (BMI).
Radiographic Review
Radiographs of all TKAs were reviewed by the treating surgeon and another senior surgeon. All implants were independently judged to be well-fixed by both surgeons.
Lymphocyte Transformation Test
The LTT was performed by a single lab (Orthopedic Analysis, Chicago, IL). Peripheral blood mononuclear cells were isolated from whole blood samples and split into two allotments – experimental, which underwent antigenic challenge, while the mononuclear cells in the control sample were not exposed to antigen. The proliferative response from the two groups was calculated by measuring the extent of [3H]-thymidine (Amersham International, Arlington Heights, IL) incorporation into DNA. Antigens used included nickel, cobalt, chromium, molybdenum, vanadium, and zirconium. The results were used to calculate the stimulation index (SI), which is the ratio of lymphocyte proliferation in the experimental sample as compared to the proliferation rate of the control sample. An SI greater than 2 was considered a positive test. The LTT+ cohort was further subdivided into mild (SI of 2 – 4), moderate (SI of 5 – 8), and highly reactive (SI of >8) as described in the Orthopedic Analysis Metal-LTT Technical Protocol.12
Immunohistochemistry Staining
Tissue specimens immediately adjacent to the CoCrNi femoral components were taken at the time of the TKA revision procedure. Formalin-fixed, paraffin-embedded tissue specimens were prepared. Histologic sections were treated with an immunohistochemistry stain (IHC) to CD4+ and CD8+ cell surface glycoproteins (NeoGenomics Laboratory Inc., Ft Myers, FL). A single pathologist, blinded to patient information, analyzed the CD4+ and CD8+ IHC stained specimens and counted lymphocytes in the sub-synovial and perivascular tissue samples. The lymphocyte counts were reported as mean CD4+ and CD8+ cells/hpf. The mean cell ratio for each cohort was calculated by finding the mean of the individual CD4+:CD8+ cell ratios of each cohort. The total CD4+:CD8+ ratio was the sum of the sub-synovial and perivascular specimens for each subject.
Histopathological Analysis
Histopathologic analysis was performed by the same blinded pathologist using the ALVAL scoring system described by Campbell et al. and utilized by Schneiderman et al.8,9 Briefly, three histological components are scored and summed: synovial lining (0-3), inflammatory infiltrate (0-4), tissue organization (0-3). The higher the score, the more severe the immune reaction. Campbell et al.13 found that revised metal-on-metal hip arthroplasties with low bearing wear and a paucity of metal particulates in the tissue, scored an average of 8.5 +/− 1.4 out of 10, consistent with an immune reaction.
Statistical Analysis
Statistical analysis was performed with statisticians at the Southern California Clinical and Translational Science Institute (SC CTSI). Patient demographics and clinical characteristics are reported using mean/standard deviation and median/interquartile range for continuous variables and count with percent for categorical variables. Given the non-normal distribution of data and small sample size, a Mann-Whitney test was used to determine the relationship and statistical significance of LTT status and CD4+ or CD8+ cells/hpf as well as for CD4+:CD8+ lymphocyte ratio. Univariate linear regression was used to obtain estimates of β(mean change in the outcome per unit change in LTT status) and to test for significant differences between LTT SI (mild, moderate, and high) and total CD4+:CD8+ ratio. The Spearman rank correlation coefficient was used to assess potential correlations between LTT SI and CD4+:CD8+ ratios, as well as total ALVAL score (or the score of the ALVAL subcomponents) and CD4+:CD8+ ratio. Statistical significance for the study was set as a two-sided alpha of 0.05 with no adjustment for multiple comparisons due the pilot nature of the study. All analyses were conducted using Stata 16 (Statacorp, College Station, TX) and GraphPad Prism version 9.0.0 for macOS (GraphPad Software, San Diego, California U.S.).
We calculated the precision with which we could estimate the mean difference in CD4+:CD8+ ratio between LTT+ and LTT− patients, assuming 18 available patients. Assuming a standard deviation for the mean difference of 20.0, we would be able to detect a mean difference between groups, with 95% confidence, within ±9.9 cells.
Results
Of the 56 patients who met inclusion criteria, we included in the study population all 6 who were LTT− and 12 age-, sex-, and BMI-matched LTT+ patients. The age in both groups was approximately 70 years, and the groups were similar with respect to sex, BMI, mean time to revision, and diabetes ( Table 1). Clinically important differences were noted between groups with respect to proportion of patients with depression (LTT+: 16.7% vs. LTT−: 83.3%) and narcotic dependence (LTT+: 33.3% vs. LTT−: 16.7%). Overall, CD4+:CD8+ ratio was higher in the LTT+ cohort for total, sub-synovial, and perivascular levels compared to the LTT− group.
Table 1.
Patient Demographics and Clinical Characteristics
| LTT+ Cohort (N=12) | LTT− Cohort (N=6) | |
|---|---|---|
| Age | 69.9 ± 7.9 (56-81) | 70 ± 7.3 (59-82) |
| Sex (Female) | 6 (50%) | 3 (50%) |
| BMI (kg/m2) | 27.9 ± 5.2 (21-36) | 27.2 ± 4.4 (20-31) |
| Mean time to revision (days) | 1140 ± 738 (344-2571) | 1165 ± 675 (390-1919) |
| Mean time to revision (years) | 3.1 ± 2.0 (0.9-8) | 3.2 ± 1.8 (1.1-5.3) |
| Diabetes (Yes) | 4.0 (33.3%) | 3.0 (33.3%) |
| Depression (Yes) | 2.0 (16.7%) | 5.0 (83.3%) |
| Narcotic dependence | 4.0 (33.3%) | 1.0 (16.7%) |
| CD4+:CD8+ IHC Cell Ratio | ||
| Total | 1.8 ± 2.5 (0-7) | 0.9 ± 0.9 (0.2-2.3) |
| Sub-synovial | 2.1 ± 3.1 (0-11) | 0.9 ± 1 (0.1-2.7) |
| Perivascular | 2.1 ± 2.2 (0-6) | 0.9 ± 1.4 (0-3.5) |
| LTT SI Reactivity to Nickel | 10.3 ± 13 (3.1-49.5) | - |
| LTT SI Reactivity | ||
| Mildly reactive (2-4) | 2 (16.7%) | - |
| Moderately reactive (5-8) | 7 (58.3%) | - |
| Highly reactive (>8) | 3 (25%) | - |
Continuous variables presented as means with standard deviation and range. Categorical variables presented as count (percent). IHC = immunohistochemical. SI = stimulation index. LTT SI categorical classification based on reactivity as described in the Ortho Analysis technical protocol.
Lymphocyte Transformation Test
The LTT+ cohort’s mean SI to nickel was 10.3 (SD 13) with a median of 5 (IQR 4.2-12.9) (Table 1). The majority of LTT+ patients exhibited moderately reactive LTT SI Reactivity.
Lymphocyte Transformation Test and Lymphocyte Immunohistochemistry
LTT status and mean CD4+ or CD8+ cells per high powered field
The relationship between LTT status (positive or negative) and the mean CD4+ or CD8+ cells per high powered field (cells/hpf) was examined overall and for sub-synovial and perivascular regions individually. There was a significant difference with respect to mean sub-synovial CD8+ cells between groups, with LTT+ patients having higher counts than those who were LTT− (LTT+: 22.0 ± 22.0, LTT−: 59.2 ± 38.7, p=0.04) and a borderline significant difference between groups with respect to total CD8+ cells, with those in the LTT− group having a higher count than those in the LTT+ group (LTT+: 33.0 ± 26.9, LTT−: 72.2 (51.9), p=0.09) (Table 2). No other significant differences between groups were noted.
Table 2:
Relationship Between LTT Status and Mean Total CD4+ or CD8+ Cells/HPF
| Mean | Median | p-value | |
|---|---|---|---|
| Total CD4+ Cells/HPF | |||
| LTT− | 55.7 (88.1) | 22.0 (13.0, 85.5) | 0.67 |
| LTT+ | 22.8 (18.0) | 20.0 (12.3, 29.8) | |
| Total CD8+ Cells/HPF | |||
| LTT− | 72.2 (51.9) | 88.0 (13.0, 104.8) | 0.09 |
| LTT+ | 33.0 (26.9) | 31.5 (11.0, 58.0) | |
| Sub-synovial CD4+ Cells/HPF | |||
| LTT− | 34.0 (39.9) | 22.0 (7.8, 54.3) | 0.30 |
| LTT+ | 13.5 (9.5) | 11.5 (6.0, 18.8) | |
| Sub-synovial CD8+ Cells/HPF | |||
| LTT− | 59.2 (38.7) | 77.0 (12.0, 90.3) | 0.04 |
| LTT+ | 22.0 (22.0) | 9.5 (4.0, 40.5) | |
| Perivascular CD4+ Cells/HPF | |||
| LTT− | 21.7 (49.2) | 0.5 (0.0, 35.8) | 0.37 |
| LTT+ | 9.3 (16.9) | 3.0 (2.0, 7.5) | |
| Perivascular CD4+ Cells/HPF | |||
| LTT− | 13.0 (27.9) | 1.5 (0.7, 20.5) | 0.56 |
| LTT+ | 11.0 (21.5) | 3.0 (1.0, 11.0) |
p-value obtained using a two-tailed Mann-Whitney test. Means are displayed with standard deviation in parentheses. Medians are shown with the first and third quartiles in parentheses. LTT+ cohort N=12 and LTT− cohort N=6.
LTT status and CD4+:CD8+ lymphocyte ratio
When examining the relationship between CD4+:CD8+ ratio and LTT status, we did not observe any statistically significant associations for total, sub-synovial, or perivascular CD4+:CD8+ ratio (p>0.05 for all, Table 3).
Table 3:
Relationship Between LTT status and CD4+:CD8+ Cell Ratio
| Mean | Median | p-value | |
|---|---|---|---|
| Total CD4+:CD8+ Ratio | |||
| LTT− | 0.9 (0.9) | 0.4 (0.3, 1.8) | 0.40 |
| LTT+ | 1.8 (2.5) | 0.7 (0.4, 2.2) | |
| Sub-synovial CD4+:CD8+ Ratio | |||
| LTT− | 0.9 (1.0) | 0.4 (0.2, 1.8) | 0.51 |
| LTT+ | 2.1 (3.1) | 0.9 (0.3, 2.3) | |
| Perivascular CD4+:CD8+ Ratio | |||
| LTT− | 0.9 (1.4) | 0.1 (0.0, 1.7) | 0.20 |
| LTT+ | 2.1 (2.2) | 1.2 (0.2, 4.0) |
p-value obtained using the Wilcoxon rank sum test. Cohort means are displayed with standard deviation in parentheses. Cohort medians are shown with first and third quartiles in parentheses. The LTT+ cohort N=12 and LTT− cohort N=6.
LTT SI and CD4+:CD8+ lymphocyte ratio
No correlations were observed between LTT SI and total, sub-synovial, or perivascular CD4+:CD8+ cell ratios (p>0.05 for all, Table 3).
LTT SI Reactivity (mild, moderate, high) and CD4+:CD8+ lymphocyte ratio
For this analysis, LTT SI was categorized as mild, moderate, and highly reactive based on previously described criteria.12 There were no statistically significant associations between mild, moderate, or highly reactive SI and total, sub-synovial, or perivascular CD4+:CD8+ (p>0.05 for all, Table 4).
Table 4:
Correlation Between LTT SI and CD4+:CD8+ Cell Ratio
| Correlation coefficient | p-value | |
|---|---|---|
| Total LTT+ SI | −0.03 | 0.93 |
| Sub-synovial LTT+ SI | 0.06 | 0.86 |
| Perivascular LTT+ SI | 0.04 | 0.91 |
Correlation coefficient obtained using Spearman correlation test. The LTT+ cohort N=12.
Lymphocyte Immunohistochemistry and Histopathologic Analysis
CD4+:CD8+ lymphocyte ratio and ALVAL score
We found no statistically significant correlations between CD4+:CD8+ ratio and total ALVAL score or the scores of its subcomponents which included synovial lining, inflammatory infiltrate, or tissue organization scores, either among those who were LTT+ (Table 5) or the population as a whole (Table 6, p>0.05 for all).
Table 5:
Univariate Association Between LTT SI and CD4+:CD8+ Cell Ratio
| Mean | Beta (95% CI) | p-value | p-trend | |
|---|---|---|---|---|
| Total CD4+:CD8+ Ratio | ||||
| Mild SI | 0.4 (0.3) | Ref | - | |
| Moderate SI | 2.5 (3.0) | 2.1 (−2.5, 6.7) | 0.33 | 0.85 |
| High SI | 1.2 (1.7) | 0.8 (−4.4, 6.1) | 0.73 | |
| Sub-synovial CD4+:CD8+ Ratio | ||||
| Mild SI | 0.4 (0.2) | Ref | - | |
| Moderate SI | 1.8 (1.6) | 1.4 (−4.4, 7.3) | 0.60 | 0.23 |
| High SI | 3.8 (6.2) | 3.4 (−3.2, 10) | 0.27 | |
| Perivascular CD4+:CD8+ Ratio | ||||
| Mild SI | 1.5 (2.1) | Ref | - | |
| Moderate SI | 2.9 (2.4) | 1.4 (−2.4, 5.2) | 0.42 | 0.46 |
| High SI | 0.4 (0.5) | −1.1 (−5.4, 3.3) | 0.59 |
Beta values and p-values obtained using linear regression. Beta interpreted as the change in the outcome (CD4+:CD8+) for each unit increase in Stimulation Index (SI). The LTT+ cohort N=12.
Table 6:
Correlation between ALVAL Score and LTT+ Total CD4+:CD8+ Cell Ratio
| Correlation coefficient | p-value | |
|---|---|---|
| Total ALVAL Score | −0.28 | 0.38 |
| Synovial Lining Score | −0.11 | 0.74 |
| Inflammatory Infiltrate Score | −0.18 | 0.58 |
| Tissue Organization Score | −0.22 | 0.50 |
Correlation coefficient obtained using Spearman correlation test. The LTT+ cohort N=12.
Discussion
Immune-mediated reactions to implants are of interest given the widespread use of implantable medical devices.4 This is the third study in a series investigating possible immune mediated failure in patients with chronic pain and/or stiff TKA with negative infectious work up and well-fixed components. We have found no relationship between LTT status and ALVAL histological scoring.9,13
Lionberger et al. reported an increase in periprosthetic CD4+ lymphocytes relative to CD8+ lymphocytes in a cohort of patients with chronically painful TKAs and a positive LTT to nickel.10 While the finding is consistent with Ni sensitization, the CD4+ lymphocyte and CD8+ lymphocyte results were reported as the sum of the individuals in the LTT+ and LTT− cohorts but did not include the individual results within each cohort. Based on these results it is unclear if lymphocyte subsets can be used to diagnose immune failure clinically in individual patients.
We found lymphocytes in periprosthetic tissue to be highly variable in number, subtype ratio, and location. This study failed to identify any relationship between CD4+ cell/hpf or CD4+:CD8+ lymphocyte ratio and LTT status, strength of LTT SI reactivity (either as categorical or continuous), or ALVAL score. This was true when examining the total lymphocyte ratio from both tissue locations together as well as when examining the sub-synovial and perivascular regions individually. Therefore, based on these findings, lymphocyte subsets alone cannot diagnosis immune failure of a TKA.
The difference between our results and those of Lionberger et al. may be related to differences in the location of periprosthetic tissue samples, IHC staining methods, and LTT SI classification. The tissue specimens in Lionberger et al. were taken from the synovial membrane directly inferior to the patella,10 whereas we analyzed tissue specimens immediately adjacent to the anterior flange of the femoral component. Different vendors were used for IHC staining. While both studies used the same lab for LTT, the studies used different SI cutoffs to indicate a positive LTT result. The current study classified an LTT+ result based on the Orthopedic Analysis lab technique guide protocol, with an LTT+ result being based on a Ni SI of 2 or greater.12 Lionberger et al., used a Ni SI of 4 or more as their criteria for an LTT+ result.10 To assess the impact of differences in Ni SI between studies, we re-analyzed the data using an SI of 4 or greater as the criterion for an LTT+ status, however, again there was no association found between LTT+ status and CD4+ or CD8+ cells/hpf or CD4+:CD8+ lymphocyte ratio.
Our study was limited by its small sample size, resulting in low power to detect small- to moderate-effects. However, these results provide effect size estimates that can be used to power larger studies. Further, our goal was to find diagnostic criteria for immune failure applicable to an individual patient. We matched LTT+ to LTT− patients with respect to age, sex, and BMI, to mitigate potentially confounding variables. Intra-operative tissue specimen was from the same location in each case, with tissue samples taken from tissue adjacent to the anterior flange of the femoral component due to its accessibility and proximity to a cobalt-chromium-nickel component. It is, however, unknown if there is an ideal location to harvest tissue specimens to diagnose an immune reaction to metal components, or if lymphocyte number and type vary by location in the knee.
Conclusion
In summary, this study failed to identify any relationship between CD4+ cell/hpf or CD4+:CD8+ lymphocyte ratio and LTT+, strength of SI reactivity (categorical or continuous), or ALVAL score. Based on these results, lymphocyte subsets in periprosthetic histological section alone cannot diagnosis immune failure of a TKA. Research is needed to identify specific, diagnostic, characteristics of immune failure in TKA. A critical management decision in cases with suspicion of an allergic reaction is whether to use hypoallergenic implants. That decision should be evidence-based.
Supplementary Material
Table 7:
Correlation Between Total ALVAL Score, ALVAL Subcomponent Scores, and Total CD4+:CD8+ Cell Ratio
| Correlation coefficient | p-value | |
|---|---|---|
| Total ALVAL Score | −0.29 | 0.24 |
| Synovial Lining Score | −0.37 | 0.13 |
| Inflammatory Infiltrate Score | −0.13 | 0.61 |
| Tissue Organization Score | −0.22 | 0.39 |
Correlation coefficient obtained using spearman correlation test. The LTT+ cohort N=12 and LTT− cohort N=6.
Table 8:
LTT− IHC Lymphocyte Subset Results
| LTT− Sub-synovial | LTT− Perivascular | LTT− Total | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Subj | CD4+ | CD8+ | CD4+:CD8+ | CD4+ | CD8+ | CD4+:CD8+ | CD4+ | CD8+ | CD4+:CD8+ |
| 1 | 234 | 143 | 1.64 | 112 | 73 | 1.53 | 122 | 70 | 1.74 |
| 2 | 16 | 92 | 0.17 | 9 | 90 | 0.10 | 7 | 2 | 3.50 |
| 3 | 36 | 85 | 0.42 | 35 | 81 | 0.43 | 1 | 4 | 0.25 |
| 4 | 4 | 15 | 0.27 | 4 | 14 | 0.29 | 0 | 1 | 0 |
| 5 | 16 | 7 | 2.29 | 16 | 6 | 2.67 | 0 | 1 | 0 |
| 6 | 28 | 91 | 0.31 | 28 | 91 | 0.31 | 0 | 0 | 0 |
Table 9:
LTT+ IHC Lymphocyte Subset Results
| LTT+ Total | LTT+ Sub-synovial | LTT+ Perivascular | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Subj | CD4+ | CD8+ | CD4+:CD8+ | CD4+ | CD8+ | CD4+:CD8+ | CD4+ | CD8+ | CD4+:CD8+ |
| 1 | 31 | 63 | 0.49 | 25 | 62 | 0.40 | 6 | 1 | 6.00 |
| 2 | 22 | 27 | 0.81 | 19 | 8 | 2.38 | 3 | 19 | 0.16 |
| 3 | 7 | 1 | 7.00 | 2 | 0 | - | 5 | 1 | 5.00 |
| 4 | 12 | 64 | 0.19 | 12 | 52 | 0.23 | 0 | 12 | 0.00 |
| 5 | 35 | 11 | 3.18 | 33 | 3 | 11.00 | 2 | 8 | 0.25 |
| 6 | 26 | 4 | 6.50 | 5 | 0 | - | 21 | 4 | 5.25 |
| 7 | 0 | 11 | 0.00 | 0 | 11 | 0.00 | 0 | 0 | - |
| 8 | 13 | 43 | 0.30 | 11 | 42 | 0.26 | 2 | 1 | 2.00 |
| 9 | 19 | 38 | 0.50 | 17 | 36 | 0.47 | 2 | 2 | 1.00 |
| 10 | 21 | 36 | 0.58 | 18 | 35 | 0.51 | 3 | 1 | 3.00 |
| 11 | 71 | 85 | 0.84 | 11 | 8 | 1.38 | 60 | 77 | 0.78 |
| 12 | 17 | 13 | 1.31 | 9 | 7 | 1.29 | 8 | 6 | 1.33 |
Highlights:
There is currently no consensus on diagnostic criteria for immune failure, an allergic reaction, to a TKA.
A recent study showed an increase in CD4+ lymphocytes compared to CD8+ lymphocytes in painful TKA that are LTT+ for Ni.
Our study found no relationship between LTT status and mean CD4+ cells/hpf or CD4+:CD8+ lymphocyte ratio.
Further, no relationship was found between LTT stimulation index and CD4+:CD8+ ratio or ALVAL score.
Based on these results, lymphocyte subsets cannot diagnosis immune failure.
Acknowledgements
Funding: This work was supported by the grants UL1TR001855 and UL1TR000130 from the National Center for Advancing Translational Science (NCATS) of the U.S. National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Funding for the IHC stains was provided by the Piedmont Foundation.
Abbreviations:
- SPT
skin patch testing
- LTT
lymphocyte transformation test
- SI
LTT stimulation index
- ALVAL
aseptic lymphocyte-dominant vasculitis-associated lesion
Footnotes
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