Milk production hormone prolactin linked to active NMOSD, study finds
Protein could influence disease activity, sensory symptoms, spine lesions
Blood levels of prolactin, a hormone mostly known for its role in milk production, are significantly elevated in people with neuromyelitis optica spectrum disorder (NMOSD) as compared with healthy adults, a study found.
Among NMOSD patients, these high prolactin levels were significantly associated with active disease, sensory-related symptoms, and more lesions, or areas of damaged tissue, as seen on an MRI.
“It is worth exploring whether appropriately correcting high prolactin levels in NMOSD patients can reduce the risk of recurrence,” the researchers wrote.
The study, “The relationship between plasma prolactin levels and clinical manifestations with neuromyelitis optica spectrum disorders,” was published in the journal Neurological Sciences.
Prolactin levels compared in 95 patients with demyelinating diseases
NMOSD is an autoimmune disease in which the immune system mistakenly produces self-reactive antibodies that attack healthy nervous system cells. This leads to inflammation, primarily in the spinal cord and in the optic nerve, which connects the eyes to the brain.
In most cases, these antibodies target aquaporin-4, known as AQP4. This is a protein found in astrocytes, a type of star-shaped cell that supports nerve cells. The resulting inflammation leads to demyelination, or the loss of myelin, which is the protective coating on nerve fibers. Ultimately, this causes nerve cell dysfunction and the onset of NMOSD symptoms.
Besides its most well-known role in breast growth and milk production, prolactin promotes myelin repair. It also has immunoregulatory properties that affect “the occurrence and development of various autoimmune diseases,” the researchers noted.
Previous studies have shown that NMOSD is three times more prevalent in women than in men, and that elevated levels of prolactin during and after pregnancy coincide with a higher relapse rate in women with NMOSD.
“This suggests that [prolactin] may play a crucial role in influencing disease activity in NMOSD,” the scientists wrote.
To find out, a team of researchers at the Fujian Medical University, in China, examined prolactin levels in blood samples collected from people participating in the Registered Cohort Study of Inflammatory Demyelination Disease (NCT04386018).
This observational study follows patients with inflammatory demyelinating diseases to provide information about clinical features, progression, antibodies, and treatment.
[Prolactin] may play a crucial role in influencing disease activity in NMOSD.
The analysis included 66 NMOSD patients, 15 people with myelin oligodendrocyte glycoprotein antibody disease, known as MOGAD, and 14 people with multiple sclerosis (MS). A group of 43 healthy people — 34 women and nine men — were included as controls.
Of those with NMOSD, 59 were women and seven were men. The MOGAD group involved three women and 12 men, and there were 10 women and four men with MS.
Both MOGAD and MS are autoimmune diseases characterized by inflammation-related myelin loss in the brain and/or spinal cord. However, they have distinct underlying mechanisms compared with NMOSD.
All but one NMOSD patient tested positive for anti-AQP4 antibodies. Moreover, the NMOSD group was older — with a mean age of 43.5 — than the other two patient groups, whose ages averaged 32.4-36.5 years. The average age of the control group was 40.6.
The mean age at symptom onset also was significantly higher among people with NMOSD — who were 38, on average — than among those with the other two diseases (28.2-29.2).
“There were no significant differences in disease duration, relapse frequency, and annual relapse rate among NMOSD, MS, and MOGAD groups,” the researchers wrote.
NMOSD patients’ prolactin levels more than double that of healthy people
In the blood, 80%-95% of prolactin exists as a single protein, known as mono prolactin. Other minor forms, which have low biological activity, consist of a dimer, or double protein, and a much larger macroprolactin, called MPRL.
NMOSD patients had the highest blood levels of total prolactin of all groups. But group differences reached statistical significance only for the NMOSD group and the healthy control group. Those with NMOSD had mean prolactin levels of 580.42 milli-international units per liter, or mIU/L, while the healthy controls had levels, on average, of 268.9.
MOGAD and MS patients also had higher total prolactin levels than controls, but this difference was not significant, according to the researchers.
Similar results were seen with levels of the mono prolactin form.
Both NMOSD and MS patients had higher blood macroprolactin levels than did healthy controls, but only the difference between NMOSD and control groups reached statistical significance.
Among the 43 blood samples tested for MPRL, seven, or 16%, had sustained high levels. According to the researchers, this suggests macroprolactinemia, a condition in which macroprolactin is the main form of prolactin in the blood, often caused by a tumor in the brain’s pituitary gland.
Regarding NMOSD patients, those with evidence of active disease had significantly elevated levels of total prolactin compared with those whose disease was stable (mean 678.69 vs. 441.66 mIU/L). Mono prolactin levels showed the same dynamics, while MPRL levels showed no such association with disease activity.
Extremely high prolactin levels — more than 1,000 mIU/L — were seen in two NMOSD patients, though MRI scans showed no signs of a pituitary tumor in either. Both experienced milk production from the breast unrelated to pregnancy or lactation.
Thoracic spine lesions seen in 64% of NMOSD patients with high prolactin
NMOSD patients with sensory abnormalities such as numbness, tingling, and itching had significantly higher levels of total prolactin than did those without these symptoms.
No significant association was found between blood prolactin levels and other NMOSD symptoms, including visual, motor, cognitive, and sleep problems.
Lesions on the thoracic section of the spinal cord, as seen on MRI scans, occurred significantly more often among NMOSD patients with high prolactin levels compared with those with low levels (63.6% vs. 36.8%). No relationships were found between prolactin levels and lesions in other parts of the nervous system.
Patients with enhancing lesions, which indicate active disease, also had significantly higher prolactin levels than those without such lesions.
“In our study, we observed that plasma [prolactin] levels in the NMOSD group were significantly higher than those in the [healthy control] group, with higher levels observed during the acute phase compared to the stable phase,” the researchers wrote.
“These findings further support the predominantly pro-inflammatory role of [prolactin] in NMOSD,” they added.
The team hypothesized that prolactin may contribute to NMOSD due to its known ability to activate B-cells. This type of immune cell produces antibodies, including the self-reactive ones that drive autoimmune diseases.
In addition, the researchers noted that bromocriptine — a treatment for conditions associated with excessive prolactin levels — showed promise in systemic lupus erythematosus, another autoimmune disease linked to higher prolactin levels.
“Therefore, it is reasonable to investigate whether bromocriptine can be used in NMOSD treatment. Further research is needed to explore this possibility,” the researchers concluded.