Monoclonal plasma cell dyscrasia: immunochemical and etiological parameters of 151 cases living in the Eastern area of Morocco

¹Laboratory of Biochemistry, Mohammed VI University Hospital, PB 4806, 60049 Oujda, Morocco, ²Faculty of Medicine and Pharmacy of Oujda, Mohammed First University, PB 4867, 60049 Oujda, Morocco, ³Laboratory of Hematology, Mohammed VI University Hospital, PB 4806, 60049 Oujda, Morocco

^&Corresponding author
Aarab Adnane, Laboratory of Biochemistry, Mohammed VI University Hospital, PB 4806, 60049 Oujda, Morocco

Introduction    

Plasma cell dyscrasias (PCD) are a heterogeneous group of diseases characterized by the expansion of monoclonal bone marrow plasma cells that produce a monoclonal immunoglobulin (M-component) [1]. These proteins are commonly referred to as monoclonal proteins, M-proteins, M spikes, paraprotiens or immunoglobulinapathies that can be detected in the serum or urine of patients. They consist of two heavy chains of the same class and 2 light chains of either kappa (κ) or lambda (λ). In some cases, plasma cells produce only free light chains (FLC) mostly detected in the urine and known as Bence-Jones proteins [2]. The spectrum of hematologic conditions capable of producing monoclonal gammopathy (MG) includes monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), plasmacytoma, Waldenström macroglobulinemia (WM), chronic lymphocytic lymphoma (CLL) and other low-grade lymphomas [3]. The generalization of the practice of protein electrophoresis, immunofixation and the improvement of the techniques used are increasingly leading to the chance discovery of a monoclonal immunoglobulin spike. Monoclonal gammopathy (MG) are common in the general population, with MGUS accounting for more than 50% of cases of MG [3-5]. In this work, we propose to study the epidemiological, immunochemical, and etiological characteristics of 151 MG cases collected at the CHU Mohammed VI Oujda, Morocco.

Methods     

Our present investigation was a retrospective study that included 151 patients with MG living in the Eastern Moroccan area in which either serum protein electrophoresis and serum and/or urine immunofixation are performed at the biochemistry department of the laboratory of Mohammed VI University Hospital in Oujda, Morocco, between January 2016 and August 2019.

Samples and methods: immunofixation record from Hydrasis 2 Scan automaton was used to identify patients. All positive blood immunofixation are selected. Serum protein electrophoresis was performed on fasted samples, taken in dry tubes after centrifugation. The appearance of each sample was noted and hemolyzed, opalescent and latescent samples was excluded. These samples were stored at +4°C and then analyzed within 2 days of receipt at the laboratory (not exceeding one week) by capillary electrophoresis technique on Capillarys 2 Flex piercing automate. The total protein determination was performed by Biuret method on Architect Ci8200 and the immunofixation of samples and urine was carried out on agarose gels, using the fully automated system of Sebia Hydrasis 2 Scan. For each patient, an analysis of the medical record was performed to collect the epidemiological characteristics of the patients and the elements of the etiological diagnosis, thus facilitating the interpretation of the different profiles since the relevant clinical information was present in more than 80% of the cases.

Diagnostics: the criteria used for the diagnosis of MM, MGUS, and plasmacytoma were those defined according to International Myeloma Working Group (IMWG) criteria [6-8]. The criteria for the diagnosis of WM disease were clinical signs, whether related to WM or not, IgM levels not relevant (often > 30 g/L), Cytopenias: possible and Spinal cord infiltration [9]. The diagnosis of lymphoma was based on histological data. The diagnosis of chronic lymphocytic leukemia (CLL) was based on the existence of blood hyperlymphocytosis and blood immunophenotyping data [10]. Table 1 provides the criteria for the diagnosis of MM and related plasma cell disorders.

Data analysis: statistical analysis was performed by calculation of percentages and arithmetic averages.

Results     

Epidemiological characteristics of patients: the central laboratory of the University Hospital Mohammed VI of Oujda is represented as a regional laboratory in the Eastern Moroccan Region and serves a population that exceeds 2,314,346 inhabitants. It is the only specialized platform to cover relevant examinations in patients with basic health coverage (RAMED). Between January 2016 and August 2019, we performed 3135 serum/urine immunofixation, and 151 cases of MG was collected. These included 85 males and 66 females. Aged from 18 to 91 years with an average age of 66 years. The most demanding services are nephrology (934 tests), internal medicine (843 tests), external (605 tests), dermatology (249 tests), neurology (106 tests) and rhumatology (103 tests). The main characteristics of the population with MG are given in the Table 2.

Immunochemical data: among the 151 cases, 78.81 % (119 cases) of these patients had a monoclonal peak revealed by electrophoresis. Seventy-five point six percent (75.6%) of them had a gamma-globulin monoclonal peak. Twenty-four point four percent (24.4%) had a monoclonal peak in beta-globulin zone and we did not observe any migrating monoclonal bands in alpha-globulin zone. Furthermore, 11.92% (18 cases) of patients had a biclonal gammopathy and 9.27% (14 cases) had hypogammaglobinemia. Regarding immunoglobulin subtypes, the most frequent monoclonal protein was IgG (65.56 %), followed by IgA class (17.88 %) and IgM (4.63 %). Moreover, 11.91% of PCD patients were free light chain positive. Kappa light chain type was found in 65.56 % and lambda in 34.44%. The electrophoretic profile and the isotype repartition in patients are given in Table 3.

Etiological diagnosis: etiologies of the identified MG are summarized in Table 4. In our study, 85.1% of patients with MM had a monoclonal globulin peak. The component was located in the gamma region in 80% of cases and 20% in the beta region. Furthermore, 5.3% of patients with MM had a biclonal gammopathy and 9.6% had hypogammaglobinemia. Regarding immunoglobulin subtypes, 70.21% of MM patients had an IgG monoclonal peak, followed by IgA (24.46%) and light chain (5.33%). In the MGUS group, 83,87% of patients had a monoclonal globulin peak. Eighty eight percent (88%) had an M spike in the gamma-globulin zone, 11 % in beta-globulin. 9.67 % of MGUS patients had biclonal and 6.45 % had a hypogammaglobinemia.

Discussion     

This study aimed to highlight the epidemiological, immunologic, and etiological of MG in Eastern Moroccan Region patients and compare our results with those of other studies. This study included 151 patients evaluated from January 2016 to August 2019. The median age was 66 years. This is similar to what was reported In the cohorts of Moroccan [11] and neighboring countries, Tunisia [12], Algeria [13], and Egypt [14], where the average age of patients was respectively: 60.21, 65, 62.96 and 58.5 years. However, it was much higher in Western nations, especially in Spain [15], Sweden [16], France [17], and England [18], the median was 73, 72, 79, and 72 years respectively. The observed differences in mean ages of patients with MG between Eastern and Western nations, may be due to the quality of life, health services and medical scientific researches, which are different in the developed and underdeveloped countries furthermore it can be attributed to the prevalence of an older population in these Western countries. A large part of our patients (89%) of our patients was above 40 years old. These results were supported by the literature data, which suggests that MG are diseases of older adults. The prevalence of MGUS increases with advancing age, 3.2% in persons over 50 years of age and 7.5% in those over 70 [3]. Incidence reaches or exceeds 10% when looking at the population aged 80 years and older. In addition, the median age at diagnosis of MM is close to 70 years [6,19].

Male dominance noted in different series of the literature is checked in our series [11,14,17,18,20]. However, other authors found that women were affected more frequently than men by MG with different sex ratios 0.91 [13], 0.82 [21]. Serum protein electrophoresis (SPEP) is an easy, inexpensive method to look for qualitative and semi-quantitative changes in the protein profile. It provides, among other things, information on the presence of MG. In the analysis of SPEP, the greatest importance should be given to the gamma globulin region, which is composed primarily of immunoglobulins. Alpha-2 and beta regions should be interpreted carefully in order not to miss IgA MG, or monoclonal free light chain gammopathy, which may migrate into the alpha-2 region requiring confirmation, by immunofixation. In our study, 119 monoclonal peaks were observed, 29 peaks migrating into the beta region, and 90 peaks were detected in the gamma globulin region. In addition, we did not observe any migrating monoclonal bands in the alpha-globulin region. As shown in Sunita Tripathy's study of 150 patients suspected of having multiple myeloma. Eighty-seven point five (87.5%) of the monoclonal bands are detected in the gamma globulin region and only 12.5% of the peaks are detected in the beta globulin region [22]. Our current findings were in agreement with those previously reported [12,21,23,24]. These observations could be explained by the fact that the gamma fraction contains the largest portion of immunoglobulins.

On the other hand, the most frequent type of immunoglobulin in the current study was IgG. It was found in 65.56 % of patients, followed by Ig A (17.88%), monoclonal light chains (11.91%), and the isotype Ig M (4.65%) which came in the last place. Distributions were consistent with a Moroccan investigation, which had been executed in Mohamed V Military Hospital of Rabat [11], not in the point of view percentage, but the order. In the latter inquiry, 63.6% of the patients were assessed with a prevalence of IgG against 16.73% of IgA, 13.54% had an Ig M monoclonal band. In addition, our subtype distributions are similar in the cohorts of neighboring countries, Tunisia [12], Algeria [13], and Egypt [14]. Nonetheless, in international data, IgM isotype was more common. For instance, in the Spain [15] and France [17], IgM prevalence was 13.6% and 31.9, respectively. This could be due to the low incidence of lymphoma in our region compared to Western countries. In addition, the particularity of immunoglobulin subtypes in our series, also found in the Moroccan report [11], is the high frequency of light chain gammapathies, which represent 11.91% and 15.85% of cases respectively. In contrast, in the international series, the frequency of this type of gammopathy ranges from 2.7 to 7.4% only [11], reflecting the high prevalence of light chain myeloma in Morocco.

In some cases, MG is a result of an underlying malignancy known as plasma cell dyscrasia. This type is usually associated with multiple myeloma (MM), amyloidosis (AL), Waldenström macroglobulinemia (WM), or solitary plasmacytoma. In other cases, it is a result of a benign clonal expansion with no symptoms; this type is referred to as MGUS [25]. MGUS is present in more than 3% of the population above the age of 50 and progresses to myeloma or related malignancy at a rate of 1% per year. In different studies, the most frequent diagnosis was MGUS than MM, WM, and others gammapathies [3,15,17]. In our cohort and different studies, MM was the most frequent diagnosis. Our patients were late diagnosed because of the lack of specialized laboratories capable of carrying the diagnosis of these diseases in our country [11-13]. The limited number of MGUS in the Moroccan series is explained by recruitment based exclusively on hospitalized patients who are generally symptomatic. Indeed, the international series, particularly European and American, include a large proportion of asymptomatic subjects who regularly make systematic assessments for check-up, which would explain the high frequency of MGUS in these series.

Conclusion     

Our study involved 151 cases of monoclonal gammopathy. In our work, we found: a clear masculine predominance; In our study and in Maghreb cohorts, the light chain disease prevalence was higher than the IgM isotype; low frequency of Waldenström's macroglobulinemia; the most common monoclonal immunoglobulin observed in our studied population was IgG, which concords with other ethnic groups; the most frequent diagnosis was MM. Prospects: limit the number of cases of incidental monoclonal gammopathy by reserving the electrophoresis of proteins to classic indications and avoiding systematic examination; setting up a national registry and reference centers specialized in the diagnosis and management of monoclonal gammopathy in our country.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

All the authors have read and agreed to the final manuscript.

Acknowledgments     

We sincerely thank Pr.Choukri Mohammed for his help. We also express our gratitude to the biochemistry laboratory team, Mohammed VI University Hospital, Oujda, Morocco.

Tables     

Table 1: diagnostic criteria for MM and related plasma cell disorders

Table 2: characteristics of the 151 patients included in the study

Table 3: distribution of M-protein isotypes among diseases with a monoclonal gammopathy

Table 4: etiologies of the 151 patients included in the study

References