Scudla V, Petrová P, Minarík J, Pika T, Budíková M, Bacovský J, Repovský S
III interní klinika Lékarské fakulty UP a FN Olomouc.
Vnitr Lek. 2010 Jun;56(6):591-601.
This study aimed to measure serum levels of 12 selected parameters in patients with monoclonal gammopathy of undetermined significance (MGUS) and initial, asymptomatic phase of multiple myeloma (MM) to assess their potential benefit in differentiating both conditions.
The analysed sample of 131 patients consisted of 62 patients with MGUS and 69 patients with MM fulfilling the criteria of the International Myeloma Working Group (IMWG). The following techniques were used to assess serum levels: quantitative immunoradiometry (bone-type alkaline phosphatase - bALP and insulin-like growth factor-1 - IGF-1), chemiluminescent enzyme immunochemical reaction (parathormone--PTH), quantitative sandwich enzyme immunoassay (osteopontin--OPN, endostatin (ES), macrophage inflammatory protein-1alpha/beta--MIP-1alpha/beta, angiogenin--ANG a IL-17). Pearson chi2 test and Mann-Whitney U-test were applied during the statistical analysis.
The analysis showed statistically significant differences in serum concentrations between MGUS and symptomatic form of MM (Durie-Salmon (D-S) stage 2-3) for: albumin, beta2-microglobulin (beta2-M) and OPN (p = 0.0001 and < 0.0001); osteocalcin for stage 2 (p = 0.006) and MIP-1alpha for stage 3 patients (p = 0.0002). Using the International Staging System (ISS), statistically significant differences between MGUS and all stages of MM (1-3) were identified for albumin and OPN (p = 0.003 and 0.001 and 0.00009, respectively), stages 2 and 3 for beta2-M and ES (p = 0.015 and 0.0001, respectively), stage 2 for ANG (p = 0.014) and stage 3 for MIP-1alpha (p = 0.00001). Statistically significant differences between MGUS and initial, asymptomatic phase of MM (D-S stage 1) was found only for bALP (p = 0.01) and for albumin (p = 0.004) and OPN (p = 0.003) when ISS was applied. Renal function impairment (D-S substage B) showed in comparison to MGUS significant elevation of serum levels of beta2-M (p < 0.0001), OC (p = 0.011), IGF-1 (p = 0.014), OPN (p = 0.003), ES (p = 0.0001), MIP-1alpha (p = 0.0004) and ANG (p = 0.005) and for albumin (p < 0.0001), beta2-M (p < 0.0001) and OPN (p < 0.0001) only when compared to substage A.
Only albumin and OPN showed useful even though non-specific potential to differentiate MGUS from all ISS stages of MM, beta2-M and ES for ISS stages 2 and 3, the other parameters differed for stage 2 (ANG), stage 3 (MIP-1alpha) only and stage 1 (bALP), stage 2 (OC) and stage 3 (MIP-1alpha) when D-S stratification was applied.
本研究旨在测量意义未明的单克隆丙种球蛋白病(MGUS)患者以及多发性骨髓瘤(MM)初始无症状阶段患者血清中12种选定参数的水平,以评估这些参数在鉴别这两种疾病方面的潜在作用。
分析的131例患者样本包括62例MGUS患者和69例符合国际骨髓瘤工作组(IMWG)标准的MM患者。采用以下技术评估血清水平:定量免疫放射测定法(骨型碱性磷酸酶 - bALP和胰岛素样生长因子 - 1 - IGF - 1)、化学发光酶免疫化学反应(甲状旁腺激素 - PTH)、定量夹心酶免疫测定法(骨桥蛋白 - OPN、内皮抑素(ES)、巨噬细胞炎性蛋白 - 1α/β - MIP - 1α/β、血管生成素 - ANG和IL - 17)。统计分析采用Pearson卡方检验和Mann - Whitney U检验。
分析显示,MGUS与有症状的MM(Durie - Salmon(D - S)分期2 - 3期)之间,血清浓度在以下参数上存在统计学显著差异:白蛋白、β2 - 微球蛋白(β2 - M)和OPN(p = 0.0001和<0.0001);2期骨钙素(p = 0.006)和3期患者的MIP - 1α(p = 0.0002)。采用国际分期系统(ISS)时,MGUS与MM所有分期(1 - 3期)之间,白蛋白和OPN存在统计学显著差异(分别为p = 0.003、0.001和0.00009),2期和3期的β2 - M和ES(分别为p = 0.015和0.0001),2期的ANG(p = 0.014)和3期的MIP - 1α(p = 0.00001)。仅采用ISS时,MGUS与MM初始无症状阶段(D - S分期1期)之间,仅bALP(p = 0.01)、白蛋白(p = 0.004)和OPN(p = 0.003)存在统计学显著差异。与MGUS相比,肾功能损害(D - S亚分期B)显示血清β2 - M(p < 0.0001)、骨钙素(OC)(p = 0.011)、IGF - 1(p = 0.014)、OPN(p = 0.003)、ES(p = 0.0001)、MIP - 1α(p = 0.0004)和ANG(p = 0.005)水平显著升高,仅与亚分期A相比时,白蛋白(p < 0.0001)、β2 - M(p < 0.0001)和OPN(p < 0.0001)也显著升高。
仅白蛋白和OPN虽不具有特异性,但在鉴别MGUS与MM的所有ISS分期方面具有一定作用,β2 - M和ES在ISS分期2期和3期有鉴别作用,其他参数仅在采用D - S分层时,2期(ANG)、3期(MIP - 1α)以及1期(bALP)、2期(OC)和3期(MIP - 1α)存在差异。